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Sample records for overcome steric barriers

  1. Overcoming Intercultural Communication Barriers.

    ERIC Educational Resources Information Center

    Hulbert, Jack E.

    1994-01-01

    Describes an activity that helps students overcome the multicultural barriers that might be encountered in dealing with people from various cultures in a global economy. Outlines instructions, reporting procedures, principles to emphasize, and time required for the exercise. (HB)

  2. OVERCOMING CULTURAL BARRIERS.

    ERIC Educational Resources Information Center

    BARRUTIA, RICHARD

    THE RELATIONSHIP OF LANGUAGE DEVELOPMENT TO CULTURAL BARRIERS AND THE TEACHING OF FOREIGN LANGUAGES IS DISCUSSED IN THIS ARTICLE. VARIOUS VIEWS OF THE MEANING OF CULTURE ARE MENTIONED IN ORDER TO SINGLE OUT ANTHROPOLOGICAL CULTURE AS A MAIN FOCAL POINT. INTERCULTURAL DIFFERENCES ARE SPELLED OUT WITH EXAMPLES OF LINGUISTIC BARRIERS, AND…

  3. Replica-exchange method in van der Waals radius space: overcoming steric restrictions for biomolecules.

    PubMed

    Itoh, Satoru G; Okumura, Hisashi; Okamoto, Yuko

    2010-04-01

    We present a new type of the Hamiltonian replica-exchange method, where the van der Waals radius parameter and not the temperature is exchanged. By decreasing the van der Waals radii, which control spatial sizes of atoms, this Hamiltonian replica-exchange method overcomes the steric restrictions and energy barriers. Furthermore, the simulation based on this method escapes from the local-minimum free-energy states and realizes effective sampling in the conformational space. We applied this method to an alanine dipeptide in aqueous solution and showed the effectiveness of the method by comparing the results with those obtained from the conventional canonical and replica-exchange methods.

  4. Overcoming barriers to patient safety.

    PubMed

    Kalisch, Beatrice J; Aebersold, Michelle

    2006-01-01

    Creating a culture of patient safety is a critical goal of all patient care unit staff. An analysis of the key barriers to patient safety on a typical inpatient unit in an acute care hospital (unclear unit values), the fear of punishment for errors, the lack of systematic analysis of mistakes, the complexity of the nurses' work, and inadequate teamwork are presented. Nine practices to overcome these barriers and achieve patient safety are discussed.

  5. Overcoming barriers to patient safety.

    PubMed

    Kalisch, Beatrice J; Aebersold, Michelle

    2006-01-01

    Creating a culture of patient safety is a critical goal of all patient care unit staff. An analysis of the key barriers to patient safety on a typical inpatient unit in an acute care hospital (unclear unit values), the fear of punishment for errors, the lack of systematic analysis of mistakes, the complexity of the nurses' work, and inadequate teamwork are presented. Nine practices to overcome these barriers and achieve patient safety are discussed. PMID:16786829

  6. Overcoming Barriers in Working with Families

    ERIC Educational Resources Information Center

    Heru, Alison M.; Drury, Laura

    2006-01-01

    Objective: The Accreditation Council for Graduate Medical Education and the Residency Review Committee for psychiatry outline the expected competencies for residents. These competencies include working with families. This article describes barriers that residents face when working with families, and offers ways to overcome these barriers. Method:…

  7. Overcoming biological barriers with ultrasound

    NASA Astrophysics Data System (ADS)

    Thakkar, Dhaval; Gupta, Roohi; Mohan, Praveena; Monson, Kenneth; Rapoport, Natalya

    2012-10-01

    Effect of ultrasound on the permeability of blood vessels and cell membranes to macromolecules and nanodroplets was investigated using mouse carotid arteries and tumor cells. Model macromolecular drug, FITC-dextran with molecular weight of 70,000 Da was used in experiments with carotid arteries. The effect of unfocused 1-MHz ultrasound and and perfluoro-15-crown-5-ether nanodroplets stabilized with the poly(ethylene oxide)-co-poly(D, L-lactide) block copolymer shells was studied. In cell culture experiments, ovarian carcinoma cells and Doxorubicin (DOX) loaded poly(ethylene oxide)-co-polycaprolactone nanodroplets were used. The data showed that the application of ultrasound resulted in permeabilization of all biological barriers tested. Under the action of ultrasound, not only FITC-dextran but also nanodroplets effectively penetrated through the arterial wall; the effect of continuous wave ultrasound was stronger than that of pulsed ultrasound. In cell culture experiments, ultrasound triggered DOX penetration into cell nuclei, presumably due to releasing the drug from the carrier. Detailed mechanisms of the observed effects require further study.

  8. Overcoming Barriers in the Media Center

    ERIC Educational Resources Information Center

    Winter, Clint

    2011-01-01

    Web 2.0 has revolutionized one's ability to teach students in new and exciting ways. Students with disabilities can now overcome many barriers that once kept them from being successful in the regular education classroom. Media specialists can effectively advocate for students with disabilities. School library media specialists have the ability to…

  9. Overcoming Barriers to Engaging in College Academics

    ERIC Educational Resources Information Center

    Hensley, Lauren; Shaulskiy, Stephanie; Zircher, Andrew; Sanders, Megan

    2015-01-01

    Underprepared college students face transition issues that prevent full academic engagement. The written responses of 176 students in a learning-strategies course were used to develop a grounded model of overcoming barriers to academic engagement. Findings revealed contexts in which academic engagement involved high costs (i.e., effort, trade-off,…

  10. Steric, Quantum, and Electrostatic Effects on SN2 Reaction Barriers in Gas Phase

    PubMed Central

    Liu, Shubin; Hu, Hao; Pedersen, Lee G.

    2010-01-01

    Biomolecular nucleophilic substitution reactions, SN2, are fundamental and commonplace in chemistry. It is the well documented experimental finding in the literature that vicinal substitution with bulkier groups near the reaction center significantly slows the reaction due to steric hindrance, but theoretical understanding in the quantitative manner about factors dictating the SN2 reaction barrier height is still controversial. In this work, employing the new quantification approach that we recently proposed for the steric effect from the density functional theory framework, we investigate the relative contribution of three independent effects, steric, electrostatic, and quantum, to the SN2 barrier heights in gas phase for substituted methyl halide systems, R1R2R3CX, reacting with fluorine anion where R1, R2, and R3 denote substituting groups and X=F or Cl. We found that in accordance with the experimental finding, for these systems the steric effect dominates the transition state barrier, contributing positively to barrier heights, but this contribution is largely compensated by the negative, stabilizing contribution from the quantum effect due to the exchange-correlation interactions. Moreover, we find that it is the component from the electrostatic effect that is linearly correlated with the SN2 barrier height for the systems investigated in the present study. In addition, we compared our approach with the conventional method of energy decomposition in density functional theory, as well as examined the steric effect from the wavefunction theory for these systems via the natural bond orbital analysis. PMID:20377265

  11. Overcoming Blocks and Barriers to Creativity.

    ERIC Educational Resources Information Center

    Raudsepp, Eugene

    1982-01-01

    Organizational barriers to creativity are examined. It is noted that resistance to change is a major impediment to creative problem solving in most organizations. Understanding the barriers to change that exist is viewed to help people exercise and develop their creativity more fully and effectively. (MP)

  12. Consumer and Employer Strategies for Overcoming Employment Barriers. Technical Report.

    ERIC Educational Resources Information Center

    Crudden, Adele; Williams, Wendy; McBroom, Lynn W.; Moore, J. Elton

    This report on strategies for overcoming employment barriers for persons with visual impairments summarizes comments and suggestions of 7 focus groups comprised of either consumers (n=49) or employers (n=19). The report first reviews the literature concerning employment barriers and how consumers in previous studies suggested these barriers be…

  13. Explaining and overcoming barriers to climate change adaptation

    NASA Astrophysics Data System (ADS)

    Eisenack, Klaus; Moser, Susanne C.; Hoffmann, Esther; Klein, Richard J. T.; Oberlack, Christoph; Pechan, Anna; Rotter, Maja; Termeer, Catrien J. A. M.

    2014-10-01

    The concept of barriers is increasingly used to describe the obstacles that hinder the planning and implementation of climate change adaptation. The growing literature on barriers to adaptation reveals not only commonly reported barriers, but also conflicting evidence, and few explanations of why barriers exist and change. There is thus a need for research that focuses on the interdependencies between barriers and considers the dynamic ways in which barriers develop and persist. Such research, which would be actor-centred and comparative, would help to explain barriers to adaptation and provide insights into how to overcome them.

  14. Overcoming Barriers to Shared Decision Making

    MedlinePlus

    ... American Heart area Search by State SELECT YOUR LANGUAGE Español (Spanish) 简体中文 (Traditional Chinese) 繁体中文 (Simplified Chinese) ... to interfere with your daily life, you may benefit from counseling, medication or both. Barrier: Difficulty understanding ...

  15. Overcoming Autopsy Barriers in Pediatric Cancer Research

    PubMed Central

    Alabran, Jennifer L.; Hooper, Jody E.; Hill, Melissa; Smith, Sandra E.; Spady, Kimberlee K.; Davis, Lara E.; Peterson, Lauren S.; Malempati, Suman; Ryan, Christopher W.; Acosta, Rae; Spunt, Sheri L.; Keller, Charles

    2012-01-01

    BACKGROUND More than 13,000 children annually in the United States and Canada under the age of 20 will be diagnosed with cancer at a mortality approaching twenty percent [1,2]. Tumor samples obtained by autopsy provide an innovative way to study tumor progression, potentially aiding in the discovery of new treatments and increased survival rates. The purpose of this study was to identify barriers to autopsies and develop guidelines for requesting autopsies for research purposes. PROCEDURE Families of children treated for childhood cancer were referred by patient advocacy groups and surveyed about attitudes and experiences with research autopsies. From 60 interviews, barriers to autopsy and tumor banking were identified. An additional 14 interviews were conducted with medical and scientific experts. RESULTS Ninety-three percent of parents of deceased children did or would have consented to a research autopsy if presented with the option; however, only half of these families were given the opportunity to donate autopsy tissue for research. The most significant barriers were the physicians’ reluctance to ask a grieving family and lack of awareness about research opportunities. CONCLUSIONS The value of donating tumor samples to research via an autopsy should be promoted to all groups managing pediatric cancer patients. Not only does autopsy tumor banking offer a potentially important medical and scientific impact, but the opportunity to contribute this Legacy Gift of autopsy tumor tissue also creates a positive outlet for the grieving family. Taking these findings into account, our multidisciplinary team has developed a curriculum addressing key barriers. PMID:23015377

  16. Dos Hermanas Chicanas: Overcoming Barriers to Professional Advancement

    ERIC Educational Resources Information Center

    Prospero, Moises

    2007-01-01

    Women and ethnic minorities face steep barriers to professional advancement, and those who rise to the executive level typically use a variety of strategies to overcome obstacles in their way. This study first reviewed the literature on barriers to professional advancement for women and ethnic minorities and the strategies that they report using…

  17. Overcoming learning barriers through knowledge management.

    PubMed

    Dror, Itiel E; Makany, Tamas; Kemp, Jonathan

    2011-02-01

    The ability to learn highly depends on how knowledge is managed. Specifically, different techniques for note-taking utilize different cognitive processes and strategies. In this paper, we compared dyslexic and control participants when using linear and non-linear note-taking. All our participants were professionals working in the banking and financial sector. We examined comprehension, accuracy, mental imagery & complexity, metacognition, and memory. We found that participants with dyslexia, when using a non-linear note-taking technique outperformed the control group using linear note-taking and matched the performance of the control group using non-linear note-taking. These findings emphasize how different knowledge management techniques can avoid some of the barriers to learners.

  18. Overcoming health literacy barriers: a model for action.

    PubMed

    Mancuso, Lorraine

    2011-01-01

    A large influx of Indonesian immigrants seeking asylum from racial and religious persecution into our hospital service area alerted providers to the need for specific cultural knowledge about this ethnic group, and to develop new skill sets to effectively care for this population. Health education programs that provide knowledge and tools to overcome misunderstandings that arise from differences between provider and client expectations for behavior will be most effective in overcoming the health literacy barriers that so often contribute to health disparities. A framework to understand factors that affect health literacy for local Indonesian asylum seekers guided community health education, while the written educational materials for programs informed providers about health literacy barriers for this population. Community outreach engaged local pastors and interpreters as cultural brokers to collaborate with nurses to develop and implement culturally sensitive programs that are socially sensitive to the local Indonesian refugee population. PMID:21744676

  19. Synergistic action of RNA polymerases in overcoming the nucleosomal barrier.

    PubMed

    Jin, Jing; Bai, Lu; Johnson, Daniel S; Fulbright, Robert M; Kireeva, Maria L; Kashlev, Mikhail; Wang, Michelle D

    2010-06-01

    During gene expression, RNA polymerase (RNAP) encounters a major barrier at a nucleosome and yet must access the nucleosomal DNA. Previous in vivo evidence has suggested that multiple RNAPs might increase transcription efficiency through nucleosomes. Here we have quantitatively investigated this hypothesis using Escherichia coli RNAP as a model system by directly monitoring its location on the DNA via a single-molecule DNA-unzipping technique. When an RNAP encountered a nucleosome, it paused with a distinctive 10-base pair periodicity and backtracked by approximately 10-15 base pairs. When two RNAPs elongate in close proximity, the trailing RNAP apparently assists in the leading RNAP's elongation, reducing its backtracking and enhancing its transcription through a nucleosome by a factor of 5. Taken together, our data indicate that histone-DNA interactions dictate RNAP pausing behavior, and alleviation of nucleosome-induced backtracking by multiple polymerases may prove to be a mechanism for overcoming the nucleosomal barrier in vivo.

  20. Evolving Drug Delivery Strategies to Overcome the Blood Brain Barrier

    PubMed Central

    Hersh, David S.; Wadajkar, Aniket S.; Roberts, Nathan B.; Perez, Jimena G.; Connolly, Nina P.; Frenkel, Victor; Winkles, Jeffrey A.; Woodworth, Graeme F.; Kim, Anthony J.

    2016-01-01

    The blood-brain barrier (BBB) poses a unique challenge for drug delivery to the central nervous system (CNS). The BBB consists of a continuous layer of specialized endothelial cells linked together by tight junctions, pericytes, nonfenestrated basal lamina, and astrocytic foot processes. This complex barrier controls and limits the systemic delivery of therapeutics to the CNS. Several innovative strategies have been explored to enhance the transport of therapeutics across the BBB, each with individual advantages and disadvantages. Ongoing advances in delivery approaches that overcome the BBB are enabling more effective therapies for CNS diseases. In this review, we discuss: (1) the physiological properties of the BBB, (2) conventional strategies to enhance paracellular and transcellular transport through the BBB, (3) emerging concepts to overcome the BBB, and (4) alternative CNS drug delivery strategies that bypass the BBB entirely. Based on these exciting advances, we anticipate that in the near future, drug delivery research efforts will lead to more effective therapeutic interventions for diseases of the CNS.

  1. Overcoming the barriers to xenotransplantation: prospects for the future

    PubMed Central

    Ekser, Burcin; Cooper, David KC

    2010-01-01

    Cross-species transplantation (xenotransplantation) has immense potential to solve the critical need for organs, tissues and cells for clinical transplantation. The increasing availability of genetically engineered pigs is enabling progress to be made in pig-to-nonhuman primate experimental models. Potent pharmacologic immunosuppressive regimens have largely prevented T-cell rejection and a T-cell-dependent elicited antibody response. However, coagulation dysfunction between the pig and primate is proving to be a major problem, and this can result in life-threatening consumptive coagulopathy. This complication is unlikely to be overcome until pigs expressing a human ‘antithrombotic’ or ‘anticoagulant’ gene, such as thrombomodulin, tissue factor pathway inhibitor or CD39, become available. Progress in islet xenotransplantation has been more encouraging, and diabetes has been controlled in nonhuman primates for periods in excess of 6 months, although this has usually been achieved using immunosuppressive protocols that might not be clinically applicable. Further advances are required to overcome the remaining barriers. PMID:20402385

  2. Overcoming the Confucian psychological barrier in government cyberspace.

    PubMed

    Lee, Ook; Gong, Sung Jin

    2004-02-01

    The Confucian tradition still dictates the behavior of many people in East Asian countries such as South Korea. Even in e-mail communication, people try their best to show signs of respect which is required by the Confucian tradition. This psychological barrier can be detrimental to the development of democracy as people are educated not to challenge opinions of elders or bosses. After a long military dictatorship, South Korea has emerged as a newly democratized nation where the Confucian tradition is less emphasized. However, this tradition dies hard, and citizens are still afraid of offending government officials who have the power to affect lives of citizens. In light of creating a more democratic society, the e-government project has been implemented, and one of the features of cyber-government is to give citizens a place in cyberspace to express their concerns. Even though citizens have to use their real names, it is found that those who wrote messages in the bulletin board of the city of Seoul government's web pages tend not to use terms that are often used in e-mails for the purpose of expressing respect. A survey was conducted, and results show that people were able to overcome the Confucian psychological barrier in government cyberspace. Self-efficacy is proposed to explain this phenomenon. PMID:15006165

  3. Better buildings by design: Overcoming barriers to efficiency

    SciTech Connect

    Lovins, A. )

    1995-01-01

    Buildings use roughly a third of the energy--and two-thirds of the electricity in the US--and, unfortunately, waste most of it. Most offices, schools, factories, shopping malls, apartment complexes, houses, and other buildings are heated, cooled, ventilated, and lit in abysmally inefficient ways--not because their developers, architects, contractors, operators, and owners were venal or stupid, but because they all faithfully did their jobs, responding to the incentives they saw. Indeed, the market in efficient building services is so imperfect that it is best described as spherically senseless--it makes no sense no matter which way you look at it. The good news--now being demonstrated by farseeing architects, developers, contractors and engineers--is that the numerous institutional barriers to efficiency can be profitably overcome. Indeed, the compelling economic and environmental advantages of better design represent a tremendously lucrative opportunity. To seize it, however, one must first understand where the barriers are, and how they can be surmounted.

  4. Overcoming entropic barrier with coupled sampling at dual resolutions.

    PubMed

    Lwin, Thur Zar; Luo, Ray

    2005-11-15

    An enhanced sampling method is proposed for ab initio protein folding simulations. The new method couples a high-resolution model for accuracy and a low-resolution model for efficiency. It aims to overcome the entropic barrier found in the exponentially large protein conformational space when a high-resolution model, such as an all-atom molecular mechanics force field, is used. The proposed method is designed to satisfy the detailed balance condition so that the Boltzmann distribution can be generated in all sampling trajectories in both high and low resolutions. The method was tested on model analytical energy functions and ab initio folding simulations of a beta-hairpin peptide. It was found to be more efficient than replica-exchange method that is used as its building block. Analysis with the analytical energy functions shows that the number of energy calculations required to find global minima and to converge mean potential energies is much fewer with the new method. Ergodic measure shows that the new method explores the conformational space more rapidly. We also studied imperfect low-resolution energy models and found that the introduction of errors in low-resolution models does decrease its sampling efficiency. However, a reasonable increase in efficiency is still observed when the global minima of the low-resolution models are in the vicinity of the global minimum basin of the high-resolution model. Finally, our ab initio folding simulation of the tested peptide shows that the new method is able to fold the peptide in a very short simulation time. The structural distribution generated by the new method at the equilibrium portion of the trajectory resembles that in the equilibrium simulation starting from the crystal structure.

  5. Overcoming the barrier of lactose intolerance to reduce health disparities.

    PubMed

    Jarvis, Judith K; Miller, Gregory D

    2002-02-01

    Federal health goals for the public have focused on reducing health disparities that exist between whites and various racial and ethnic groups. Many of the chronic diseases for which African Americans are at greater risk- hypertension, stroke, colon cancer, and obesity-may be exacerbated by a low intake of calcium and/or other dairy-related nutrients. For example, a low intake of dairy food nutrients, such as calcium, potassium, and magnesium, may contribute to the high risk of hypertension seen in African Americans. The Dietary Approaches to Stop Hypertension (DASH) study demonstrated that a low-fat diet rich in fruits and vegetables (8 to 10 servings) and low-fat dairy foods (3 servings) significantly reduced blood pressure-and was twice as effective in African-American participants. Calcium and dairy food consumption is particularly low among African-American, Hispanic, and Asian populations. Average intakes are near the threshold of 600 to 700 mg/day, below which bone loss and hypertension can result. Although lactose intolerance may be partly to blame for the low calcium intakes due to reduced dairy food consumption by minority populations, culturally determined food preferences and dietary practices learned early in life also play a role. The high incidence figures for primary lactose maldigestion among minority groups grossly overestimates the number who will experience intolerance symptoms after drinking a glass of milk with a meal. Randomized, double-blind, controlled clinical trials have demonstrated that by using a few simple dietary strategies, those who maldigest lactose (have low levels of the lactase enzyme) can easily tolerate a dairy-rich diet that meets calcium intake recommendations. Physicians and other health professionals can help their minority patients and the general public understand how to improve calcium nutrition by overcoming the surmountable barrier of lactose intolerance. At the same time they will be helping to reduce the incidence

  6. Overcoming Barriers to Wind Development in Appalachian Coal Country

    SciTech Connect

    Brent Bailey; Evan Hansen

    2012-10-09

    This research project synthesizes existing data and communication from experts to assess barriers to wind development in Pennsylvania, Maryland, West Virginia, Virginia, and Kentucky, and makes recommendations where feasible to reduce or eliminate those barriers.

  7. Psychology of Success: Overcoming Barriers to Pursuing Further Education

    ERIC Educational Resources Information Center

    Goto, Stanford T.; Martin, Connie

    2009-01-01

    Of the many barriers that prevent adults from continuing their education, psychological barriers are least often addressed by educators. This is an important area of concern because psychological factors influence how prospective students respond to other barriers. This qualitative study was conducted to describe how adults negotiate…

  8. 75 FR 58347 - Information Collection; Overcoming Barriers to Wildland Fire Defensible Space Behaviors

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-24

    ...; ] DEPARTMENT OF AGRICULTURE Forest Service Information Collection; Overcoming Barriers to Wildland Fire... Fire Defensible Space Behaviors. DATES: Comments must be received in writing on or before November 23...: Overcoming Barriers to Wildland Fire Defensible Space Behaviors. OMB Number: 0596-New. Type of Request:...

  9. SOLUTIONS TO OVERCOME BARRIERS TO IMPLEMENTATION OF TREATMENT TECHNOLOGIES

    EPA Science Inventory

    To make treatment a viable option for remediation you must first identify the barriers to implementing treatment. The primary barrier is economics. Treatment options are relatively expensive and there is a lack of funds for treatment. The cost of technologies can be lowered by 1)...

  10. Provider barriers to telemental health: obstacles overcome, obstacles remaining.

    PubMed

    Brooks, Elizabeth; Turvey, Carolyn; Augusterfer, Eugene F

    2013-06-01

    Many providers are hesitant to use telemental health technologies. When providers are queried, various barriers are presented, such as the clinician's skepticism about the effectiveness of telemental health (TMH), viewing telehealth technologies as inconvenient, or reporting difficulties with medical reimbursement. Provider support for TMH is critical to its diffusion because clinicians often serve as the initial gatekeepers to telehealth implementation and program success. In this article, we address provider concerns in three broad domains: (1) personal barriers, (2) clinical workflow and technology barriers, and (3) licensure, credentialing, and reimbursement barriers. We found evidence that, although many barriers have been discussed in the literature for years, advancements in TMH have rapidly reduced obstacles for its use. Improvements include extensive opportunities for training, a growing evidence base supporting positive TMH outcomes, and transformations in technologies that improve provider convenience and transmission quality. Recommendations for further change are discussed within each domain. In particular, it is important to grow and disseminate data underscoring the promise and effectiveness of TMH, integrate videoconferencing capabilities into electronic medical record platforms, expand TMH reimbursement, and modify licensure standards.

  11. Overcoming Barriers to Generalism in Medicine: The Residents' Perspective.

    ERIC Educational Resources Information Center

    Steiner, Elizabeth; Stoken, Jacqueline M.

    1995-01-01

    This paper presents medical residents' opinions regarding barriers to producing more generalist physicians, such as lack of appropriate training in ambulatory generalist practice and the increased prestige given to specialists. Recommendations are offered to medical schools, residency programs, the community, and the culture of medicine to…

  12. Automation U.S.A.: Overcoming Barriers to Automation.

    ERIC Educational Resources Information Center

    Brody, Herb

    1985-01-01

    Although labor unions and inadequate technology play minor roles, the principal barrier to factory automation is "fear of change." Related problems include long-term benefits, nontechnical executives, and uncertainty of factory cost accounting. Industry support for university programs is helping to educate engineers to design, implement, and…

  13. Jumping Deadfall: Overcoming Barriers to Implementing Outdoor and Environmental Education.

    ERIC Educational Resources Information Center

    Hanna, Glenda

    This paper discusses some of the common barriers confronting outdoor and experiential education teachers and presents strategies for surmounting them. The identified concerns and suggested solutions were obtained from in-depth open-ended interviews conducted with 10 outdoor education/environmental education consultants and teachers in Alberta…

  14. Women in School Administration: Overcoming the Barriers to Advancement.

    ERIC Educational Resources Information Center

    WEEA Digest, 1990

    1990-01-01

    This digest examines three prominent theories that attempt to explain why women are underrepresented in educational administration and develops a three-dimensional matrix as an empowerment perspective. Each of the theories--resocialization, structural barriers, and male dominance--is based on deficiencies in the woman, the system, or the society.…

  15. Why and how to prescribe exercise: overcoming the barriers.

    PubMed

    Fletcher, Gerald; Trejo, Jorge F

    2005-08-01

    Exercise helps prevent and improve atherosclerosis and other chronic diseases, and physicians should encourage their patients to exercise more. Unfortunately, there are many barriers to prescribing exercise. To help patients start exercising and stay with it, clinicians need to address specifics. Several guidelines are available to achieve this goal.

  16. Adolescents' Self-Efficacy to Overcome Barriers to Physical Activity Scale

    ERIC Educational Resources Information Center

    Dwyer, John J. M.; Chulak, Tala; Maitland, Scott; Allison, Kenneth R.; Lysy, Daria C.; Faulkner, Guy E. J.; Sheeshka, Judy

    2012-01-01

    This paper describes a revised measure of self-efficacy to overcome barriers to moderate and vigorous physical activity in a sample of 484 high school students in Toronto, Ontario. The students had a mean age of 15.3 years. Principal axis factoring with oblique rotation yielded five factors: self-efficacy to overcome internal, harassment, physical…

  17. No One Is Unemployable: Creative Solutions for Overcoming Barriers to Employment.

    ERIC Educational Resources Information Center

    Harney, Elisabeth E.

    The goal of the WorkNet Model Career Development & Job Placement for people with barriers is to help even the most challenged job seekers begin and advance in careers they enjoy. This paper presents one key component of the WorkNet Model, a practical process for creatively overcoming any barrier a candidate faces. The chapter includes: the…

  18. Overcoming the barriers to using kangaroo care in neonatal settings.

    PubMed

    Penn, Sarah

    2015-06-01

    Skin-to-skin contact, or kangaroo care (KC), has benefits for babies and parents, improving clinical outcomes, temperature control, breastfeeding rates and child-parent bonding; it reduces morbidity and mortality. Barriers to KC for neonates may include a lack of training for nurses, lack of time, maternal or child physical or mental ill health, and inappropriate settings. With education and helpful management, neonatal nurses can advocate for KC for all babies. Parents may need information and encouragement to begin with. Therefore, nurses can improve the experiences of their patients and, in the long run, free time to perform clinical procedures.

  19. Overcoming barriers to public understanding of climate change

    NASA Astrophysics Data System (ADS)

    Hayhoe, K.

    2012-12-01

    Humans are interfering with global climate, increasing the risk of serious consequences for human society and the natural environment. As the scientific evidence builds, however, so does the public controversy surrounding this issue. Why is climate change so contentious? What makes it so hard to comprehend? I argue that there is no single reason for this, but rather a perfect storm of multiple confounding factors; scientific, historical, ideological, psychological and even physiological in nature. Education—of both the messengers and the audience—can play a critical role in surmounting many of the common barriers to understanding, accepting, and acting this important issue.

  20. Recognizing and overcoming potential barriers to oral medications for MS.

    PubMed

    Moses, Harold

    2014-10-01

    Three FDA-approved oral medications are available for the treatment of relapsing forms of multiple sclerosis: fingolimod, teriflunomide, and dimethyl fumarate. While injection and IV treatments have proven to be beneficial, these newer oral agents also offer positive outcomes for patients. Numerous barriers exist, though, for these oral agents, including the unknown long-term efficacy and safety and potential side effects. Despite possible side effects, oral agents provide convenience, ease of use, and the elimination of injection/IV administration-site pain. To ensure MS patients receive the most appropriate individualized care, clinicians should present all of the available treatment options to both newly diagnosed and established patients. PMID:25373133

  1. Newborn screening progress in developing countries--overcoming internal barriers.

    PubMed

    Padilla, Carmencita D; Krotoski, Danuta; Therrell, Bradford L

    2010-04-01

    Newborn screening is an important public health measure aimed at early identification and management of affected newborns thereby lowering infant morbidity and mortality. It is a comprehensive system of education, screening, follow-up, diagnosis, treatment/management, and evaluation that must be institutionalized and sustained within public health systems often challenged by economic, political, and cultural considerations. As a result, developing countries face unique challenges in implementing and expanding newborn screening that can be grouped into the following categories: (1) planning, (2) leadership, (3) medical support, (4) technical support, (5) logistical support, (6) education, (7) protocol and policy development, (8) administration, (9) evaluation, and (10) sustainability. We review some of the experiences in overcoming implementation challenges in developing newborn screening programs, and discuss recent efforts to encourage increased newborn screening through support networking and information exchange activities in 2 regions-the Asia Pacific and the Middle East/North Africa. PMID:20207264

  2. Barriers to overcome for effective cancer control in Africa.

    PubMed

    Harford, Joe B

    2015-08-01

    Cancer control in Africa is complicated due to large differences in cancer incidence between countries caused by differences in exposure to known risk factors. For example, substantial differences are seen when selected cancers in north Africa are compared with those in sub-Saharan Africa. In the future, population growth and demographic shifts are likely to have profound effects on the prevalence of cancer across the continent. Likewise, many factors outside of health care such as language differences, conflict, and poverty can affect cancer control efforts. Although cooperation in cancer control efforts is desirable, differences in cultural and geopolitical factors that characterise African countries and their populations, together with the sheer size of the continent, present unique challenges to effective cancer control. This Series paper discusses factors related to the size, diversity, and conditions within Africa that present barriers to optimal collaboration in cancer control efforts across the continent. PMID:26248846

  3. Rethinking technology, revitalizing ethics: overcoming barriers to ethical design.

    PubMed

    Feng, P

    2000-04-01

    This paper explores the role of ethics in design. Traditionally, ethical questions have been seen as marginal issues in the design of technology. Part of the reason for this stems from the widely held notion of technology being "out of control." This notion is a barrier to what I call "ethical design" because it implies that ethics has no role to play in the development of technology. This view, however, is challenged by recent work in the field of Science and Technology Studies (STS). Looking into the dynamics of technological change, STS scholars argue that human choices are present at every stage of a technology's development and, furthermore, that human values are reflected in the very design of artifacts. This alternative view suggests that ethics can and should be included in the design process. Drawing on examples from the privacy arena, I point to some of the potential advantages of addressing ethical concerns early on in the design of a technology. I conclude with some general strategies for bringing ethics back into design.

  4. Understanding and overcoming barriers to human papillomavirus vaccine acceptance.

    PubMed

    Zimet, Gregory D

    2006-02-01

    New vaccines designed to prevent human papillomavirus (HPV) infection have the potential to reduce the incidence of serious illness and death worldwide among women, substantially reduce the emotional suffering associated with abnormal Papanicolaou (Pap) test results and the diagnosis of cervical cancer, and save significant health care dollars. However, these benefits may not be fully realized until the vaccine is accepted by patients, parents, and health care practitioners. Furthermore, there may be unique issues related to the acceptance of a vaccine designed to prevent a sexually transmitted infection that is poorly understood by many women. Among the acceptance issues are: individual comfort with a sexually transmitted infection (STI) vaccine; parental comfort with vaccination of their preadolescent/early adolescent daughters; physician comfort with recommending a human papillomavirus vaccine to women and parents of preadolescents; and physician communication skills related to talking with women and parents about the vaccine. Potentially difficult as it might be to implement a vaccination program, vaccination and prevention of HPV-associated disease are still infinitely preferable to observation and treatment. This article will review some of the potential barriers to HPV Vaccine acceptance, with a particular focus on factors relevant to female patients, parents, and health care providers.

  5. Mentoring women in academic surgery: overcoming institutional barriers to success.

    PubMed

    Hoover, Eddie L

    2006-09-01

    Women now comprise 50% of Caucasian matriculants to medical school; 66.6% of African Americans, 48% of Hispanics and 51.3% of Asians beginning medical school are also women. This trend is likely to continue since women now earn 57% of all undergraduate degrees, and they earn more degrees in the health professions and biological sciences than men. Black and Hispanic women now earn 66% and 60% of bachelor's degrees in their respective ethnic groups. Overall, women are concentrated at the lowest faculty ranks at medical schools, with 70% holding the rank of instructor or assistant professor. Women continue to experience difficulty with recruitment, retention, promotion and pay issues compared to men. They also experience additional gender-specific issues, including primary responsibility for rearing families and quality-of-life issues in some specialties, including most of the surgical disciplines. Clearly, there is an evolving population shift at work here; the pool of candidates for medical school faculty positions is likely to be evenly split between men and women for Caucasians, Hispanics and Asians, while the African-American pool is likely heavily weighted in favor of the women. Women are beginning to garner more Latin honors recognition at graduation as well and the definition of the "best and the brightest" is being redefined. Therefore, institutions must continue to identify the barriers that deter women from entering surgery, to develop research tools to understand how to improve the process of developing leadership skills among women and to insure a "buy-in" of their male counterparts when components of the plan are being implemented. PMID:17019926

  6. Mentoring women in academic surgery: overcoming institutional barriers to success.

    PubMed

    Hoover, Eddie L

    2006-09-01

    Women now comprise 50% of Caucasian matriculants to medical school; 66.6% of African Americans, 48% of Hispanics and 51.3% of Asians beginning medical school are also women. This trend is likely to continue since women now earn 57% of all undergraduate degrees, and they earn more degrees in the health professions and biological sciences than men. Black and Hispanic women now earn 66% and 60% of bachelor's degrees in their respective ethnic groups. Overall, women are concentrated at the lowest faculty ranks at medical schools, with 70% holding the rank of instructor or assistant professor. Women continue to experience difficulty with recruitment, retention, promotion and pay issues compared to men. They also experience additional gender-specific issues, including primary responsibility for rearing families and quality-of-life issues in some specialties, including most of the surgical disciplines. Clearly, there is an evolving population shift at work here; the pool of candidates for medical school faculty positions is likely to be evenly split between men and women for Caucasians, Hispanics and Asians, while the African-American pool is likely heavily weighted in favor of the women. Women are beginning to garner more Latin honors recognition at graduation as well and the definition of the "best and the brightest" is being redefined. Therefore, institutions must continue to identify the barriers that deter women from entering surgery, to develop research tools to understand how to improve the process of developing leadership skills among women and to insure a "buy-in" of their male counterparts when components of the plan are being implemented.

  7. Coherent anti-Stokes Raman scattering microscopy: overcoming technical barriers for clinical translation.

    PubMed

    Tu, Haohua; Boppart, Stephen A

    2014-01-01

    Clinical translation of coherent anti-Stokes Raman scattering microscopy is of great interest because of the advantages of noninvasive label-free imaging, high sensitivity, and chemical specificity. For this to happen, we have identified and review the technical barriers that must be overcome. Prior investigations have developed advanced techniques (features), each of which can be used to effectively overcome one particular technical barrier. However, the implementation of one or a small number of these advanced features in previous attempts for clinical translation has often introduced more tradeoffs than benefits. In this review, we outline a strategy that would integrate multiple advanced features to overcome all the technical barriers simultaneously, effectively reduce tradeoffs, and synergistically optimize CARS microscopy for clinical translation. The operation of the envisioned system incorporates coherent Raman micro-spectroscopy for identifying vibrational biomolecular markers of disease and single-frequency (or hyperspectral) Raman imaging of these specific biomarkers for real-time in vivo diagnostics and monitoring.

  8. Overcoming Barriers to Skills Training in Borderline Personality Disorder: A Qualitative Interview Study

    PubMed Central

    Barnicot, Kirsten; Couldrey, Laura; Sandhu, Sima; Priebe, Stefan

    2015-01-01

    Despite evidence suggesting that skills training is an important mechanism of change in dialectical behaviour therapy, little research exploring facilitators and barriers to this process has been conducted. The study aimed to explore clients’ experiences of barriers to dialectical behaviour therapy skills training and how they felt they overcame these barriers, and to compare experiences between treatment completers and dropouts. In-depth qualitative interviews were conducted with 40 clients with borderline personality disorder who had attended a dialectical behaviour therapy programme. A thematic analysis of participants’ reported experiences found that key barriers to learning the skills were anxiety during the skills groups and difficulty understanding the material. Key barriers to using the skills were overwhelming emotions which left participants feeling unable or unwilling to use them. Key ways in which participants reported overcoming barriers to skills training were by sustaining their commitment to attending therapy and practising the skills, personalising the way they used them, and practising them so often that they became an integral part of their behavioural repertoire. Participants also highlighted a number of key ways in which they were supported with their skills training by other skills group members, the group therapists, their individual therapist, friends and family. Treatment dropouts were more likely than completers to describe anxiety during the skills groups as a barrier to learning, and were less likely to report overcoming barriers to skills training via the key processes outlined above. The findings of this qualitative study require replication, but could be used to generate hypotheses for testing in further research on barriers to skills training, how these relate to dropout, and how they can be overcome. The paper outlines several such suggestions for further research. PMID:26465757

  9. Overcoming Barriers to Skills Training in Borderline Personality Disorder: A Qualitative Interview Study.

    PubMed

    Barnicot, Kirsten; Couldrey, Laura; Sandhu, Sima; Priebe, Stefan

    2015-01-01

    Despite evidence suggesting that skills training is an important mechanism of change in dialectical behaviour therapy, little research exploring facilitators and barriers to this process has been conducted. The study aimed to explore clients' experiences of barriers to dialectical behaviour therapy skills training and how they felt they overcame these barriers, and to compare experiences between treatment completers and dropouts. In-depth qualitative interviews were conducted with 40 clients with borderline personality disorder who had attended a dialectical behaviour therapy programme. A thematic analysis of participants' reported experiences found that key barriers to learning the skills were anxiety during the skills groups and difficulty understanding the material. Key barriers to using the skills were overwhelming emotions which left participants feeling unable or unwilling to use them. Key ways in which participants reported overcoming barriers to skills training were by sustaining their commitment to attending therapy and practising the skills, personalising the way they used them, and practising them so often that they became an integral part of their behavioural repertoire. Participants also highlighted a number of key ways in which they were supported with their skills training by other skills group members, the group therapists, their individual therapist, friends and family. Treatment dropouts were more likely than completers to describe anxiety during the skills groups as a barrier to learning, and were less likely to report overcoming barriers to skills training via the key processes outlined above. The findings of this qualitative study require replication, but could be used to generate hypotheses for testing in further research on barriers to skills training, how these relate to dropout, and how they can be overcome. The paper outlines several such suggestions for further research.

  10. Overcoming Barriers to Skills Training in Borderline Personality Disorder: A Qualitative Interview Study.

    PubMed

    Barnicot, Kirsten; Couldrey, Laura; Sandhu, Sima; Priebe, Stefan

    2015-01-01

    Despite evidence suggesting that skills training is an important mechanism of change in dialectical behaviour therapy, little research exploring facilitators and barriers to this process has been conducted. The study aimed to explore clients' experiences of barriers to dialectical behaviour therapy skills training and how they felt they overcame these barriers, and to compare experiences between treatment completers and dropouts. In-depth qualitative interviews were conducted with 40 clients with borderline personality disorder who had attended a dialectical behaviour therapy programme. A thematic analysis of participants' reported experiences found that key barriers to learning the skills were anxiety during the skills groups and difficulty understanding the material. Key barriers to using the skills were overwhelming emotions which left participants feeling unable or unwilling to use them. Key ways in which participants reported overcoming barriers to skills training were by sustaining their commitment to attending therapy and practising the skills, personalising the way they used them, and practising them so often that they became an integral part of their behavioural repertoire. Participants also highlighted a number of key ways in which they were supported with their skills training by other skills group members, the group therapists, their individual therapist, friends and family. Treatment dropouts were more likely than completers to describe anxiety during the skills groups as a barrier to learning, and were less likely to report overcoming barriers to skills training via the key processes outlined above. The findings of this qualitative study require replication, but could be used to generate hypotheses for testing in further research on barriers to skills training, how these relate to dropout, and how they can be overcome. The paper outlines several such suggestions for further research. PMID:26465757

  11. Measuring women's perceived ability to overcome barriers to healthcare seeking in Burkina Faso

    PubMed Central

    2012-01-01

    Background In sub-Saharan Africa, women must overcome numerous barriers when they need modern healthcare. Respect of gender norms within the household and the community may still influence women's ability to obtain care. A lack of gender-sensitive instruments for measuring women's ability to overcome barriers compromises attempts to adequately quantify the burden and risk of exclusion they face when seeking modern healthcare. The aim of this study was to create and validate a synthetic measure of women's access to healthcare from a publicly available and possibly internationally comparable population-based survey. Method Seven questionnaire items from the Burkina Faso 2003 DHS were combined to create the index. Cronbach's alpha coefficient was used to test the reliability of the index. Exploratory factor analyses (EFA) and confirmatory factor analyses (CFA) were applied to evaluate the factorial structure and construct validity of the index while taking into account the hierarchical structure of the data. Results The index has a Cronbach's alpha of 0.75, suggesting adequate reliability. In EFA, three correlated factors fitted the data best. In CFA, the construct of perceived ability to overcome barriers to healthcare seeking emerged as a second-order latent variable with three domains: socioeconomic barriers, geographical barriers and psychosocial barriers. Model fit indices support the index's global validity for women of reproductive age in Burkina Faso. Evidence for construct validity comes from the finding that women's index scores increase with household living standard. Conclusion The DHS items can be combined into a reliable and valid, gender-sensitive index quantifying reproductive-age women's perceived ability to overcome barriers to healthcare seeking in Burkina Faso. The index complies conceptually with the sector-cross-cutting capability approach and enables measuring directly the perceived access to healthcare. Therefore it can help to improve the

  12. Strategies for Overcoming Key Barriers to Development of a National Security Workforce

    SciTech Connect

    2008-06-30

    This report documents the strategies for overcoming identified key barriers to development of an adequate national security workforce as part of the National Security Preparedness Project (NSPP) being performed under a Department of Energy (DOE) National Nuclear Security Administration (NNSA) grant. Many barriers currently exist that prevent the development of an adequate number of properly trained national security personnel. The identified strategies to address the barriers will focus on both short-term and long-term efforts, as well as strategies to capture legacy knowledge of retiring national security workforce personnel.

  13. Powering Your Community With Solar: Overcoming Market and Implementation Barriers (Fact Sheet)

    SciTech Connect

    Not Available

    2012-06-01

    This document introduces the Energy Department's new Solarize Guidebook: A Community Guide to Collective Purchasing of Residential PV Systems. The guide is designed for 'green' consumers, utilities, local governments, and community groups who want to replicate the success of the Solarize Portland model, overcome barriers to implementation, and permanently transform the market for solar energy in their communities.

  14. Using Appropriate Digital Tools to Overcome Barriers to Collaborative Learning in Classrooms

    ERIC Educational Resources Information Center

    Wardlow, Liane; Harm, Eian

    2015-01-01

    Collaborative learning provides students with vital opportunities to create and build knowledge. Existing technologies can facilitate collaborative learning. However, barriers exist to enacting collaborative practices related to the coverage of material for assessments and classroom management concerns, among others. Teachers can overcome these…

  15. Building America Guidance for Identifying and Overcoming Code, Standard, and Rating Method Barriers

    SciTech Connect

    Cole, P. C.; Halverson, M. A.

    2013-09-01

    This guidance document was prepared using the input from the meeting summarized in the draft CSI Roadmap to provide Building America research teams and partners with specific information and approaches to identifying and overcoming potential barriers to Building America innovations arising in and/or stemming from codes, standards, and rating methods.

  16. Overcoming barriers to exercise among parents: a social cognitive theory perspective.

    PubMed

    Mailey, Emily L; Phillips, Siobhan M; Dlugonski, Deirdre; Conroy, David E

    2016-08-01

    Parents face numerous barriers to exercise and exhibit high levels of inactivity. Examining theory-based determinants of exercise among parents may inform interventions for this population. The purpose of this study was to test a social-cognitive model of parental exercise participation over a 12-month period. Mothers (n = 226) and fathers (n = 70) of children <16 completed measures of exercise, barriers self-efficacy, perceived barriers, and exercise planning at baseline and 1 year later. Panel analyses were used to test the hypothesized relationships. Barriers self-efficacy was related to exercise directly and indirectly through perceived barriers and prioritization/planning. Prioritization and planning also mediated the relationship between perceived barriers and exercise. These paths remained significant at 12 months. These results suggest efforts to increase exercise in parents should focus on improving confidence to overcome exercise barriers, reducing perceptions of barriers, and helping parents make specific plans for prioritizing and engaging in exercise.

  17. Emergency department crowding, part 2--barriers to reform and strategies to overcome them.

    PubMed

    Moskop, John C; Sklar, David P; Geiderman, Joel M; Schears, Raquel M; Bookman, Kelly J

    2009-05-01

    Part 1 of this 2-article series reviews serious moral problems created by emergency department (ED) crowding. In this second part of the series, we identify and describe operational and financial barriers to resolving the crisis of ED crowding, along with a variety of institutional and public policy strategies proposed or implemented to overcome those barriers. Finally, the article evaluates 2 additional actions designed to address the problem of ED crowding, namely, distribution of a warning statement to ED patients and implementation of a "reverse triage" system for safe early discharge of hospital inpatients. PMID:19027194

  18. Overcoming transport barriers for interstitial-, lymphatic-, and lymph node-targeted drug delivery

    PubMed Central

    Thomas, Susan N.; Schudel, Alex

    2015-01-01

    Despite drug formulation improving circulation times and targeting, efficacy is stymied by inadequate penetration into and retention within target tissues. This review highlights the barriers restricting delivery to the connective tissue interstitium, lymphatics, and lymph nodes as well as advances in engineering drug carriers to overcome these delivery challenges. Three-dimensional tissue physiology is discussed in the context of providing material design principles for delivery to these tissues; in particular the influence of interstitial and lymphatic flows as well as differential permeabilities of the blood and lymphatic capillaries. Key examples of materials with different characteristics developed to overcome these transport barriers are discussed as well as potential areas for further development. PMID:25745594

  19. Public Health in the Emergency Department: Overcoming Barriers to Implementation and Dissemination

    PubMed Central

    McKay, Mary Pat; Vaca, Federico E.; Field, Craig; Rhodes, Karin

    2011-01-01

    This article is the outcome of a consensus building workshop entitled, “Overcoming Barriers to Implementation and Dissemination” convened at the 2009 Academic Emergency Medicine Consensus Conference, “Public Health in the ED: Surveillance, Screening, and Intervention.” The participants were asked to address potential methods for overcoming barriers to the dissemination and implementation in the emergency department (ED) of evidenced-based practices to improve public health. The panel discussed three broad areas of interest including methods for disseminating evidence-based practices, barriers encountered during the process of implementation, and the importance of involvement in activities outside the ED including engagement in policy development and improvement. Four recommendations were discussed in detail and consensus was reached. The recommendations included 1) researchers and advocates should disseminate findings through multiple forums beyond peer-reviewed publications when an ED-based public health intervention has enough evidence to support integration into the routine practice of emergency care; 2) local barriers to implementation of public health interventions should be recognized and well understood from multiple perspectives prior to implementation; 3) innovation must be put into place and adapted based on local institutional context and culture as barriers and the best methods for overcoming them will vary across institutions; and 4) use of legislation, regulation, and incentives outside of the ED should support and strengthen ED-based interventions. For each area of interest, research dimensions to extend the current understanding of methods for effectively and efficiently implementing evidence-based public health interventions in the ED were discussed and consensus was achieved. PMID:20053233

  20. The Role of Carrier Geometry in Overcoming Biological Barriers to Drug Delivery.

    PubMed

    Jordan, Carolyn; Shuvaev, Vladimir V; Bailey, Mark; Muzykantov, Vladimir R; Dziubla, Thomas D

    2016-01-01

    For a variety of diseases, effective therapy is severely limited or rendered impossible due to an inability to deliver medications to the intended sites of action. Multiple barriers exist through the body, which have evolved over time to limit the migration of foreign compounds from entering the tissues. Turning toward biology as inspiration, it has been the general goal of drug delivery to create carrier strategies that mimic, in part, features of bacteria/ viruses that allow them overcome these barriers. By packaging drugs into nano and micron scale vehicles, it should be possible to completely change the biodistribution and residence times of pharmaceutically active compounds. Recently, due to advances in formulation technologies, it has become possible to control not just the material selection, surface chemistry, and/or size, but also the overall geometry and plasticity of the drug carriers. These approaches aid in the formulation of nonspherical particles such as, discs, rods, and even unique structures such as cubes and nanodiamonds. The adjustment of size and shape can be used for the aid or prevention in cellular uptake and also to overcome the vascular and mucosal barrier. In this review, we present a summary of some approaches used to control carrier shape and the impact these geometries have upon drug transport across biological barriers.

  1. The Role of Carrier Geometry in Overcoming Biological Barriers to Drug Delivery.

    PubMed

    Jordan, Carolyn; Shuvaev, Vladimir V; Bailey, Mark; Muzykantov, Vladimir R; Dziubla, Thomas D

    2016-01-01

    For a variety of diseases, effective therapy is severely limited or rendered impossible due to an inability to deliver medications to the intended sites of action. Multiple barriers exist through the body, which have evolved over time to limit the migration of foreign compounds from entering the tissues. Turning toward biology as inspiration, it has been the general goal of drug delivery to create carrier strategies that mimic, in part, features of bacteria/ viruses that allow them overcome these barriers. By packaging drugs into nano and micron scale vehicles, it should be possible to completely change the biodistribution and residence times of pharmaceutically active compounds. Recently, due to advances in formulation technologies, it has become possible to control not just the material selection, surface chemistry, and/or size, but also the overall geometry and plasticity of the drug carriers. These approaches aid in the formulation of nonspherical particles such as, discs, rods, and even unique structures such as cubes and nanodiamonds. The adjustment of size and shape can be used for the aid or prevention in cellular uptake and also to overcome the vascular and mucosal barrier. In this review, we present a summary of some approaches used to control carrier shape and the impact these geometries have upon drug transport across biological barriers. PMID:26675218

  2. Mental health care for irregular migrants in Europe: Barriers and how they are overcome

    PubMed Central

    2012-01-01

    Background Irregular migrants (IMs) are exposed to a wide range of risk factors for developing mental health problems. However, little is known about whether and how they receive mental health care across European countries. The aims of this study were (1) to identify barriers to mental health care for IMs, and (2) to explore ways by which these barriers are overcome in practice. Methods Data from semi-structured interviews with 25 experts in the field of mental health care for IMs in the capital cities of 14 European countries were analysed using thematic analysis. Results Experts reported a range of barriers to mental health care for IMs. These include the absence of legal entitlements to health care in some countries or a lack of awareness of such entitlements, administrative obstacles, a shortage of culturally sensitive care, the complexity of the social needs of IMs, and their fear of being reported and deported. These barriers can be partly overcome by networks of committed professionals and supportive services. NGOs have become important initial points of contact for IMs, providing mental health care themselves or referring IMs to other suitable services. However, these services are often confronted with the ethical dilemma of either acting according to the legislation and institutional rules or providing care for humanitarian reasons, which involves the risk of acting illegally and providing care without authorisation. Conclusions Even in countries where access to health care is legally possible for IMs, various other barriers remain. Some of these are common to all migrants, whilst others are specific for IMs. Attempts at improving mental health care for IMs should consider barriers beyond legal entitlement, including communicating information about entitlement to mental health care professionals and patients, providing culturally sensitive care and ensuring sufficient resources. PMID:22607386

  3. "Closing the Loop": Overcoming barriers to locally sourcing food in Fort Collins, Colorado

    NASA Astrophysics Data System (ADS)

    DeMets, C. M.

    2012-12-01

    Environmental sustainability has become a focal point for many communities in recent years, and restaurants are seeking creative ways to become more sustainable. As many chefs realize, sourcing food locally is an important step towards sustainability and towards building a healthy, resilient community. Review of literature on sustainability in restaurants and the local food movement revealed that chefs face many barriers to sourcing their food locally, but that there are also many solutions for overcoming these barriers that chefs are in the early stages of exploring. Therefore, the purpose of this research is to identify barriers to local sourcing and investigate how some restaurants are working to overcome those barriers in the city of Fort Collins, Colorado. To do this, interviews were conducted with four subjects who guide purchasing decisions for restaurants in Fort Collins. Two of these restaurants have created successful solutions and are able to source most of their food locally. The other two are interested in and working towards sourcing locally but have not yet been able to overcome barriers, and therefore only source a few local items. Findings show that there are four barriers and nine solutions commonly identified by each of the subjects. The research found differences between those who source most of their food locally and those who have not made as much progress in local sourcing. Based on these results, two solution flowcharts were created, one for primary barriers and one for secondary barriers, for restaurants to assess where they are in the local food chain and how they can more successfully source food locally. As there are few explicit connections between this research question and climate change, it is important to consider the implicit connections that motivate and justify this research. The question of whether or not greenhouse gas emissions are lower for locally sourced food is a topic of much debate, and while there are major developments

  4. Designing Caregiver-Implemented Shared-Reading Interventions to Overcome Implementation Barriers

    PubMed Central

    Logan, Jessica R.; Damschroder, Laura

    2015-01-01

    Purpose This study presents an application of the theoretical domains framework (TDF; Michie et al., 2005), an integrative framework drawing on behavior-change theories, to speech-language pathology. Methods A multistep procedure was used to identify barriers affecting caregivers' implementation of shared-reading interventions with their children with language impairment (LI). The authors examined caregiver-level data corresponding to implementation issues from two randomized controlled trials and mapped these to domains in the TDF as well as empirically validated behavior-change techniques. Results Four barriers to implementation were identified as potentially affecting caregivers' implementation: time pressures, reading difficulties, discomfort with reading, and lack of awareness of benefits. These were mapped to 3 TDF domains: intentions, beliefs about capabilities, and skills. In turn, 4 behavior-change techniques were identified as potential vehicles for affecting these domains: reward, feedback, model, and encourage. An ongoing study is described that is determining the effects of these techniques for improving caregivers' implementation of a shared-reading intervention. Conclusions A description of the steps to identifying barriers to implementation, in conjunction with an ongoing experiment that will explicitly determine whether behavior-change techniques affect these barriers, provides a model for how implementation science can be used to identify and overcome implementation barriers in the treatment of communication disorders. PMID:26262941

  5. Overcoming Recruitment Barriers in Urban Older Adults Residing in Congregate Living Facilities

    PubMed Central

    Simning, Adam; van Wijngaarden, Edwin

    2015-01-01

    Background. Participation of minority older adults in mental health research has been limited by mistrust, transportation difficulties, lack of knowledge, and insufficient community partnership. We describe strategies utilized to overcome these recruitment barriers. Methods. Our target population included 553 public housing residents of older adult high-rise buildings in Rochester, NY. We had a two-stage cross-sectional study: Stage 1 was a health survey for all residents and Stage 2 was a psychiatric interview of English-speaking residents aged 60 years and older. Recruitment occurred through mailings, onsite activities, and resident referrals. Results. Stage 1 had 358 participants (64.7% response) and Stage 2 had 190 (61.6% target population response), with higher participation among African Americans. We found some strategies effective for overcoming recruitment barriers. First, we partnered with a community agency and organized onsite educational activities to improve residents' trust. Second, the study occurred entirely onsite, which facilitated participation of functionally impaired residents. Third, onsite activities allowed the residents to learn about the study and complete surveys in person. Fourth, we provided immediate incentives that resulted in many study referrals. Conclusions. Although recruitment of minority older adults presents unique challenges, a multifaceted community-tailored approach mitigated several recruitment barriers in this mental health study. PMID:26106598

  6. Geothermal(Ground-Source)Heat Pumps: Market Status, Barriers to Adoption, and Actions to Overcome Barriers

    SciTech Connect

    Hughes, Patrick

    2008-12-01

    More effective stewardship of our resources contributes to the security, environmental sustainability, and economic well-being of the nation. Buildings present one of the best opportunities to economically reduce energy consumption and limit greenhouse gas emissions. Geothermal heat pumps (GHPs), sometimes called ground-source heat pumps, have been proven capable of producing large reductions in energy use and peak demand in buildings. However, GHPs have received little attention at the policy level as an important component of a national strategy. Have policymakers mistakenly overlooked GHPs, or are GHPs simply unable to make a major contribution to the national goals for various reasons? This brief study was undertaken at DOE's request to address this conundrum. The scope of the study includes determining the status of global GHP markets and the status of the GHP industry and technology in the United States, assembling previous estimates of GHP energy savings potential, identifying key barriers to application of GHPs, and identifying actions that could accelerate market adoption of GHPs. The findings are documented in this report along with conclusions and recommendations.

  7. Strategies to overcome the barrier: use of nanoparticles as carriers and modulators of barrier properties.

    PubMed

    Rempe, Ralf; Cramer, Sandra; Qiao, Ruirui; Galla, Hans-Joachim

    2014-03-01

    The blood-brain barrier (BBB) protects the brain from toxic substances within the bloodstream and keeps the brain's homeostasis stable. On the other hand, it also represents the main obstacle in the treatment of many CNS diseases. Among different techniques, nanoparticles have emerged as promising tools to enhance brain drug delivery of therapeutic molecules. For successful drug delivery, nanoparticles may either modulate BBB integrity or exploit transport systems present on the endothelium. In this review, we present two different nanoparticles to enhance brain drug delivery. Poly(butyl cyanoacrylate) nanoparticles were shown to induce a reversible disruption of the BBB in vitro which may be exploited by simultaneous injection of the drug in question. By coating the poly(butyl cyanoacrylate) nanoparticles with, e.g., ApoE, it is also possible to circumvent the BBB via the LDL-receptor. Another example of the use of receptor-mediated endocytosis to enhance brain uptake of nanoparticles are poly(ethylene glycol)-coated Fe3O4 nanoparticles which are covalently attached to lactoferrin. These nanoparticles have been shown to facilitate the transport via the lactoferrin receptor, and so could then be used for magnetic resonance imaging.

  8. Delivery of nucleic acids for cancer gene therapy: overcoming extra- and intra-cellular barriers.

    PubMed

    McErlean, Emma M; McCrudden, Cian M; McCarthy, Helen O

    2016-09-01

    The therapeutic potential of cancer gene therapy has been limited by the difficulty of delivering genetic material to target sites. Various biological and molecular barriers exist which need to be overcome before effective nonviral delivery systems can be applied successfully in oncology. Herein, various barriers are described and strategies to circumvent such obstacles are discussed, considering both the extracellular and intracellular setting. Development of multifunctional delivery systems holds much promise for the progression of gene delivery, and a growing body of evidence supports this approach involving rational design of vectors, with a unique molecular architecture. In addition, the potential application of composite gene delivery platforms is highlighted which may provide an alternative delivery strategy to traditional systemic administration. PMID:27582234

  9. Overcoming cultural barriers to diabetes control: a qualitative study of southwestern New Mexico Hispanics.

    PubMed

    McCloskey, Joanne; Flenniken, Donna

    2010-01-01

    This qualitative study examined the impact of cultural barriers on self-management of diabetes among Hispanic participants in LA VIDA (Lifestyle and Values Impact Diabetes Awareness), a diabetes intervention program in southwestern New Mexico. As part of the LA VIDA program evaluation, in depth interviews were conducted with 50 Hispanics who had participated in one or more activities, including diabetes education classes, grocery store tours, and support groups, and who had interacted with promotores (community health workers). LA VIDA participants reported that a sense of empowerment and increased self-efficacy enabled them to overcome cultural barriers related to the traditional Hispanic diet, lack of social support, and denial about having diabetes. PMID:20860336

  10. Overcoming barriers to high performance seismic design using lessons learned from the green building industry

    NASA Astrophysics Data System (ADS)

    Glezil, Dorothy

    NEHRP's Provisions today currently governing conventional seismic resistant design. These provisions, though they ensure the life-safety of building occupants, extensive damage and economic losses may still occur in the structures. This minimum performance can be enhanced using the Performance-Based Earthquake Engineering methodology and passive control systems like base isolation and energy dissipation systems. Even though these technologies and the PBEE methodology are effective reducing economic losses and fatalities during earthquakes, getting them implemented into seismic resistant design has been challenging. One of the many barriers to their implementation has been their upfront costs. The green building community has faced some of the same challenges that the high performance seismic design community currently faces. The goal of this thesis is to draw on the success of the green building industry to provide recommendations that may be used overcome the barriers that high performance seismic design (HPSD) is currently facing.

  11. Overcoming Codes and Standards Barriers to Innovations in Building Energy Efficiency

    SciTech Connect

    Cole, Pamala C.; Gilbride, Theresa L.

    2015-02-15

    In this journal article, the authors discuss approaches to overcoming building code barriers to energy-efficiency innovations in home construction. Building codes have been a highly motivational force for increasing the energy efficiency of new homes in the United States in recent years. But as quickly as the codes seem to be changing, new products are coming to the market at an even more rapid pace, sometimes offering approaches and construction techniques unthought of when the current code was first proposed, which might have been several years before its adoption by various jurisdictions. Due to this delay, the codes themselves can become barriers to innovations that might otherwise be helping to further increase the efficiency, comfort, health or durability of new homes. . The U.S. Department of Energy’s Building America, a program dedicated to improving the energy efficiency of America’s housing stock through research and education, is working with the U.S. housing industry through its research teams to help builders identify and remove code barriers to innovation in the home construction industry. The article addresses several approaches that builders use to achieve approval for innovative building techniques when code barriers appear to exist.

  12. Overcoming barriers to diabetes care: Perceived communication issues of healthcare professionals attending a pilot Diabetes UK training programme.

    PubMed

    Mosely, Kylie; Aslam, Aysha; Speight, Jane

    2010-02-01

    As part of our evaluation of the Diabetes UK Careline workshop "Overcoming barriers to diabetes care", we received feedback from 18 healthcare professionals. Generally, they felt competent in identifying patients' psychosocial issues but less knowledgeable/skilled in handling them. Lack of time, privacy and support were barriers to addressing patients' psychosocial concerns.

  13. Nanocomplexes for gene therapy of respiratory diseases: Targeting and overcoming the mucus barrier.

    PubMed

    Di Gioia, Sante; Trapani, Adriana; Castellani, Stefano; Carbone, Annalucia; Belgiovine, Giuliana; Craparo, Emanuela Fabiola; Puglisi, Giovanni; Cavallaro, Gennara; Trapani, Giuseppe; Conese, Massimo

    2015-10-01

    Gene therapy, i.e. the delivery and expression of therapeutic genes, holds great promise for congenital and acquired respiratory diseases. Non-viral vectors are less toxic and immunogenic than viral vectors, although they are characterized by lower efficiency. However, they have to overcome many barriers, including inflammatory and immune mediators and cells. The respiratory and airway epithelial cells, the main target of these vectors, are coated with a layer of mucus, which hampers the effective reaching of gene therapy vectors carrying either plasmid DNA or small interfering RNA. This barrier is thicker in many lung diseases, such as cystic fibrosis. This review summarizes the most important advancements in the field of non-viral vectors that have been achieved with the use of nanoparticulate (NP) systems, composed either of polymers or lipids, in the lung gene delivery. In particular, different strategies of targeting of respiratory and airway lung cells will be described. Then, we will focus on the two approaches that attempt to overcome the mucus barrier: coating of the nanoparticulate system with poly(ethylene glycol) and treatment with mucolytics. Our conclusions are: 1) Ligand and physical targeting can direct therapeutic gene expression in specific cell types in the respiratory tract; 2) Mucopenetrating NPs are endowed with promising features to be useful in treating respiratory diseases and should be now advanced in pre-clinical trials. Finally, we discuss the development of such polymer- and lipid-based NPs in the context of in vitro and in vivo disease models, such as lung cancer, as well as in clinical trials. PMID:26192479

  14. Overcoming Barriers: Adolescents’ Experiences Using a Mobile Phone Dietary Assessment App

    PubMed Central

    Svensson, Åsa; Magnusson, Maria

    2016-01-01

    Background The use of new technology has the potential to increase participation rates in dietary studies and improve the validity of collected dietary data. However, to evaluate the usability of developed dietary methods, qualitative studies of participants’ experiences and perceptions are needed. Objective To explore adolescents’ experiences using a newly developed mobile phone dietary assessment app, with a focus on factors that could affect their recording of dietary intake. Methods Focus group interviews were conducted with 75 participants who had used a newly developed mobile phone dietary assessment app in a quantitative evaluation study. The interviews were analyzed using qualitative content analysis and the theoretical framework of Self Determination Theory was applied. Results The adolescents’ use of the mobile phone dietary assessment app was characterized by their struggle to overcome several perceived barriers. Facilitators that helped adolescents complete the method were also identified. Motivation was found to be an important facilitator, and intrinsically motivated participants completed the method because they found it fun to use. The autonomous extrinsically motivated participants completed the method for the greater good, in order to contribute to the study. The controlled extrinsically motivated participants completed the method to get a reward or avoid punishment. Amotivated participants did not complete the method. More motivated participants were assumed to be more able to overcome barriers and needed less facilitators. Conclusions Future studies that examine the recording of food intake should include systematic efforts that aim to minimize identified barriers and promote identified facilitators. Further research should specifically aim at studying methods for (and effects of) increasing intrinsic motivation by supporting autonomy, competence, and relatedness among adolescents asked to participate in dietary studies. PMID:27473462

  15. Nanocomplexes for gene therapy of respiratory diseases: Targeting and overcoming the mucus barrier.

    PubMed

    Di Gioia, Sante; Trapani, Adriana; Castellani, Stefano; Carbone, Annalucia; Belgiovine, Giuliana; Craparo, Emanuela Fabiola; Puglisi, Giovanni; Cavallaro, Gennara; Trapani, Giuseppe; Conese, Massimo

    2015-10-01

    Gene therapy, i.e. the delivery and expression of therapeutic genes, holds great promise for congenital and acquired respiratory diseases. Non-viral vectors are less toxic and immunogenic than viral vectors, although they are characterized by lower efficiency. However, they have to overcome many barriers, including inflammatory and immune mediators and cells. The respiratory and airway epithelial cells, the main target of these vectors, are coated with a layer of mucus, which hampers the effective reaching of gene therapy vectors carrying either plasmid DNA or small interfering RNA. This barrier is thicker in many lung diseases, such as cystic fibrosis. This review summarizes the most important advancements in the field of non-viral vectors that have been achieved with the use of nanoparticulate (NP) systems, composed either of polymers or lipids, in the lung gene delivery. In particular, different strategies of targeting of respiratory and airway lung cells will be described. Then, we will focus on the two approaches that attempt to overcome the mucus barrier: coating of the nanoparticulate system with poly(ethylene glycol) and treatment with mucolytics. Our conclusions are: 1) Ligand and physical targeting can direct therapeutic gene expression in specific cell types in the respiratory tract; 2) Mucopenetrating NPs are endowed with promising features to be useful in treating respiratory diseases and should be now advanced in pre-clinical trials. Finally, we discuss the development of such polymer- and lipid-based NPs in the context of in vitro and in vivo disease models, such as lung cancer, as well as in clinical trials.

  16. Teams, tribes and patient safety: overcoming barriers to effective teamwork in healthcare.

    PubMed

    Weller, Jennifer; Boyd, Matt; Cumin, David

    2014-03-01

    Modern healthcare is delivered by multidisciplinary, distributed healthcare teams who rely on effective teamwork and communication to ensure effective and safe patient care. However, we know that there is an unacceptable rate of unintended patient harm, and much of this is attributed to failures in communication between health professionals. The extensive literature on teams has identified shared mental models, mutual respect and trust and closed-loop communication as the underpinning conditions required for effective teams. However, a number of challenges exist in the healthcare environment. We explore these in a framework of educational, psychological and organisational challenges to the development of effective healthcare teams. Educational interventions can promote a better understanding of the principles of teamwork, help staff understand each other's roles and perspectives, and help develop specific communication strategies, but may not be sufficient on their own. Psychological barriers, such as professional silos and hierarchies, and organisational barriers such as geographically distributed teams, can increase the chance of communication failures with the potential for patient harm. We propose a seven-step plan to overcome the barriers to effective team communication that incorporates education, psychological and organisational strategies. Recent evidence suggests that improvement in teamwork in healthcare can lead to significant gains in patient safety, measured against efficiency of care, complication rate and mortality. Interventions to improve teamwork in healthcare may be the next major advance in patient outcomes.

  17. Barriers to the Uptake of Human-based Test Methods, and How to Overcome Them.

    PubMed

    Archibald, Kathy; Drake, Tamara; Coleman, Robert

    2015-11-01

    Although there is growing concern as to the questionable value of animal-based methods for determining the safety and efficacy of new medicines, which has in turn led to many groups developing innovative human-based methods, there are many barriers to their adoption for regulatory submissions. The reasons for this are various, and include a lack of confidence that the available human-based methods, be they in vivo, in silico or in vitro, can be sufficiently predictive of clinical outcomes. However, this is not the only problem: the issue of validation presents a serious impediment to progress, a particularly frustrating situation, in view of the fact that the existing animal-based methods have never themselves been formally validated. Superimposed upon this is the issue of regulatory requirements, where, although regulators may be willing to accept non-animal approaches in place of particular animal tests, nowhere is this explicitly stated in their guidelines. Such problems are far from trivial, and represent major hurdles to be overcome. In addition, there are a range of other barriers, real or self-imposed, that are hindering a more-predictive approach to establishing a new drug's clinical safety and efficacy profiles. Some of these barriers are identified, and ways forward are suggested.

  18. Physicochemical properties of polymers: An important system to overcome the cell barriers in gene transfection.

    PubMed

    Namvar, Ali; Bolhassani, Azam; Khairkhah, Niloofardokht; Motevalli, Fatemeh

    2015-07-01

    Delivery of the macromolecules including DNA, miRNA, and antisense oligonucleotides is typically mediated by carriers due to the large size and negative charge. Different physical (e.g., gene gun or electroporation), and chemical (e.g., cationic polymer or lipid) vectors have been already used to improve the efficiency of gene transfer. Polymer-based DNA delivery systems have attracted special interest, in particular via intravenous injection with many intra- and extracellular barriers. The recent progress has shown that stimuli-responsive polymers entitled as multifunctional nucleic acid vehicles can act to target specific cells. These nonviral carriers are classified by the type of stimulus including reduction potential, pH, and temperature. Generally, the physicochemical characterization of DNA-polymer complexes is critical to enhance the transfection potency via protection of DNA from nuclease digestion, endosomal escape, and nuclear localization. The successful clinical applications will depend on an exact insight of barriers in gene delivery and development of carriers overcoming these barriers. Consequently, improvement of novel cationic polymers with low toxicity and effective for biomedical use has attracted a great attention in gene therapy. This article summarizes the main physicochemical and biological properties of polyplexes describing their gene transfection behavior, in vitro and in vivo. In this line, the relative efficiencies of various cationic polymers are compared.

  19. Peptide modules for overcoming barriers of nucleic acids transport to cells.

    PubMed

    Egorova, Anna A; Kiselev, Anton V

    2016-01-01

    Absence of safe and efficient methods of nucleic acids delivery is one of the major issues which limits the development of human gene therapy. Highly efficient viral vectors raise questions due to safety reasons. Among non-viral vectors peptide-based carriers can be considered as good candidates for the development of "artificial viruses"--multifunctional polyplexes that mimic viruses. Suggested strategy to obtain multifunctionality is to combine several peptide modules into one modular carrier. Different kinds of peptide modules are needed for successful overcoming barriers of nucleic acids transport into the cells. Design of such modules and establishment of structure-function relationships are issues of importance to researchers working in the field of nucleic acids delivery.

  20. Building America Guidance for Identifying and Overcoming Code, Standard, and Rating Method Barriers

    SciTech Connect

    Cole, Pamala C.; Halverson, Mark A.

    2013-09-01

    The U.S. Department of Energy’s (DOE) Building America program implemented a new Codes and Standards Innovation (CSI) Team in 2013. The Team’s mission is to assist Building America (BA) research teams and partners in identifying and resolving conflicts between Building America innovations and the various codes and standards that govern the construction of residences. A CSI Roadmap was completed in September, 2013. This guidance document was prepared using the information in the CSI Roadmap to provide BA research teams and partners with specific information and approaches to identifying and overcoming potential barriers to Building America (BA) innovations arising in and/or stemming from codes, standards, and rating methods. For more information on the BA CSI team, please email: CSITeam@pnnl.gov

  1. Can security-enhancing interventions overcome psychological barriers to responsiveness in couple relationships?

    PubMed

    Mikulincer, Mario; Shaver, Phillip R; Sahdra, Baljinder K; Bar-On, Naama

    2013-01-01

    Recent studies have shown that both dispositional and experimentally enhanced attachment security facilitate compassion and altruism. Here we report findings from a laboratory experiment, replicated in two countries (Israel and the United States), testing the hypotheses that (a) increased security (accomplished through subliminal priming) fosters caregiving behavior toward a romantic partner who discloses a personal problem, and (b) this increased security overcomes barriers to responsiveness induced by mental depletion. We gathered data on participants' attachment insecurities, randomly assigned them to one of four mental depletion (yes, no) and priming (security, neutral) conditions, and coded their behavior in an interaction with their romantic partner who was disclosing a personal problem. Dispositional attachment insecurities and manipulated mental depletion adversely affected caregiving, but security priming overrode the detrimental effects of both mental depletion and attachment insecurity in both Israel and the United States.

  2. Overcoming the barriers to implementation of TQM/CQI in hospitals: myths and realities.

    PubMed

    Wakefield, D S; Wakefield, B J

    1993-03-01

    Many health care organizations are attempting to rapidly implement total quality management (TQM) and continuous quality improvement (CQI) philosophies and concepts. In the case of hospitals, a number of issues resulting from traditional organizational design and management practices as well as the characteristics of health care professionals pose significant challenges to rapid implementation. Recognizing and developing strategies to address these challenges, along with realizing that TQM and CQI represent viable processes for conducting organizational "preventive maintenance," may help in changing the focus of quality assessment and enhancement initiatives from processes that are "broken" to processes that should be "fixed" before they "break." This article discusses strategies for overcoming some of the major barriers and challenges to successful TQM and CQI implementation to the hospital setting.

  3. Cronobacter sakazakii clinical isolates overcome host barriers and evade the immune response.

    PubMed

    Almajed, Faisal S; Forsythe, Stephen J

    2016-01-01

    Cronobacter sakazakii is the most frequently clinically isolated species of the Cronobacter genus. However the virulence factors of C. sakazakii including their ability to overcome host barriers remains poorly studied. In this study, ten clinical isolates of C. sakazakii were assessed for their ability to invade and translocate through human colonic carcinoma epithelial cells (Caco-2) and human brain microvascular endothelial cells (HBMEC). Their ability to avoid phagocytosis in human macrophages U937 and human brain microglial cells was investigated. Additionally, they were tested for serum sensitivity and the presence of the Cronobacter plasminogen activation gene (cpa) gene, which is reported to confer serum resistance. Our data showed that the clinical C. sakazakii strains invaded and translocated through Caco-2 and HBMEC cell lines and some strains showed significantly higher levels of invasion and translocation. Moreover, C. sakazakii was able to persist and even multiply in phagocytic macrophage and microglial cells. All strains, except one, were able to withstand human serum exposure, the single serum sensitive strain was also the only one which did not encode for the cpa gene. These results demonstrate that C. sakazakii clinical isolates are able to overcome host barriers and evade the host immune response indicating their capacity to cause diseases such as necrotizing enterocolitis (NEC) and meningitis. Our data showed for the first time the ability of C. sakazakii clinical isolates to survive and multiply within human microglial cells. Additionally, it was shown that C. sakazakii clinical strains have the capacity to translocate through the Caco-2 and HBMEC cell lines paracellularly.

  4. Overcoming Barriers in Kidney Health-Forging a Platform for Innovation.

    PubMed

    Linde, Peter G; Archdeacon, Patrick; Breyer, Matthew D; Ibrahim, Tod; Inrig, Jula K; Kewalramani, Reshma; Lee, Celeste Castillo; Neuland, Carolyn Y; Roy-Chaudhury, Prabir; Sloand, James A; Meyer, Rachel; Smith, Kimberly A; Snook, Jennifer; West, Melissa; Falk, Ronald J

    2016-07-01

    Innovation in kidney diseases is not commensurate with the effect of these diseases on human health and mortality or innovation in other key therapeutic areas. A primary cause of the dearth in innovation is that kidney diseases disproportionately affect a demographic that is largely disenfranchised, lacking sufficient advocacy, public attention, and funding. A secondary and likely consequent cause is that the existing infrastructure supporting nephrology research pales in comparison with those for other internal medicine specialties, especially cardiology and oncology. Citing such inequities, however, is not enough. Changing the status quo will require a coordinated effort to identify and redress the existing deficits. Specifically, these deficits relate to the need to further develop and improve the following: understanding of the disease mechanisms and pathophysiology, patient engagement and activism, clinical trial infrastructure, and investigational clinical trial designs as well as coordinated efforts among critical stakeholders. This paper identifies potential solutions to these barriers, some of which are already underway through the Kidney Health Initiative. The Kidney Health Initiative is unique and will serve as a current and future platform from which to overcome these barriers to innovation in nephrology.

  5. Highly compacted biodegradable DNA nanoparticles capable of overcoming the mucus barrier for inhaled lung gene therapy.

    PubMed

    Mastorakos, Panagiotis; da Silva, Adriana L; Chisholm, Jane; Song, Eric; Choi, Won Kyu; Boyle, Michael P; Morales, Marcelo M; Hanes, Justin; Suk, Jung Soo

    2015-07-14

    Gene therapy has emerged as an alternative for the treatment of diseases refractory to conventional therapeutics. Synthetic nanoparticle-based gene delivery systems offer highly tunable platforms for the delivery of therapeutic genes. However, the inability to achieve sustained, high-level transgene expression in vivo presents a significant hurdle. The respiratory system, although readily accessible, remains a challenging target, as effective gene therapy mandates colloidal stability in physiological fluids and the ability to overcome biological barriers found in the lung. We formulated highly stable DNA nanoparticles based on state-of-the-art biodegradable polymers, poly(β-amino esters) (PBAEs), possessing a dense corona of polyethylene glycol. We found that these nanoparticles efficiently penetrated the nanoporous and highly adhesive human mucus gel layer that constitutes a primary barrier to reaching the underlying epithelium. We also discovered that these PBAE-based mucus-penetrating DNA nanoparticles (PBAE-MPPs) provided uniform and high-level transgene expression throughout the mouse lungs, superior to several gold standard gene delivery systems. PBAE-MPPs achieved robust transgene expression over at least 4 mo following a single administration, and their transfection efficiency was not attenuated by repeated administrations, underscoring their clinical relevance. Importantly, PBAE-MPPs demonstrated a favorable safety profile with no signs of toxicity following intratracheal administration.

  6. Understanding and Overcoming Barriers to Upper Limb Surgical Reconstruction After Tetraplegia: The Need for Interdisciplinary Collaboration.

    PubMed

    Punj, Vandana; Curtin, Catherine

    2016-06-01

    There are approximately 300,000 persons with spinal cord injury living in the United States, and nearly 60% of these persons have suffered tetraplegia with resultant alterations in body function, activity, and therefore participation. Restoring hand function can improve independence, and various studies have shown that persons with tetraplegia rate restoration of arm and hand function higher than bowel and bladder control, walking, or sexuality. There are conservative options to improve upper limb function in this population (eg, orthoses, neuroprostheses). Surgical interventions are also available, and 70% of surgical patients report satisfaction and improvement in various activities of daily living after surgery to restore arm and hand function. Despite these positive surgical outcomes, <10% of the eligible population of 60% to 70% undergo tendon transfer surgery to restore function. Underutilization of surgical interventions can be explained by population-, provider-, and health care systems-specific barriers. With further education of providers and patients and team building across disciplines these barriers can be overcome, ultimately leading to reduced disability and improved quality of life for persons with tetraplegia. PMID:27233595

  7. Creating sustainable local health information exchanges: can barriers to stakeholder participation be overcome?

    PubMed

    Grossman, Joy M; Kushner, Kathryn L; November, Elizabeth A

    2008-02-01

    Local health information exchanges (HIEs) hold the promise of collecting patient clinical data across sites of care to provide more complete and timely information for treatment, as well as supporting quality improvement and reporting, public health activities, and clinical research. Findings from a study of stakeholder perspectives on participation in four HIEs by the Center for Studying Health System Change (HSC) and the National Institute for Health Care Management (NIHCM) Foundation suggest, however, that barriers to achieving data exchange remain high. Concerns about loss of competitive advantage and data misuse impede provider and health plan willingness to contribute patient data. Additionally, uncertainty about who benefits from HIEs is affecting stakeholder willingness to fund the exchanges. The more mature exchanges--Cincinnati-based HealthBridge and the Indiana Health Information Exchange (IHIE)--have achieved some viability by meeting a specific business need--more efficient delivery of hospital test results to physicians. The newer exchanges--CareSpark, serving northeast Tennessee and southwest Virginia, and the Tampa Bay Regional Health Information Organization (RHIO)--have struggled to identify and finance initial services without a similar critical mass of hospital participation. While narrow data exchange efforts that improve transaction efficiency may be a pragmatic first step to overcome barriers to stakeholder participation, expanding HIEs to achieve the broad-based data exchange necessary for quality reporting and pay-for-performance (P4P) activities raises more challenges.

  8. Electrical, magnetic, photomechanical and cavitational waves to overcome skin barrier for transdermal drug delivery.

    PubMed

    Wong, Tin Wui

    2014-11-10

    Transdermal drug delivery is hindered by the barrier property of the stratum corneum. It limits the route to transport of drugs with a log octanol-water partition coefficient of 1 to 3, molecular weight of less than 500Da and melting point of less than 200°C. Active methods such as iontophoresis, electroporation, sonophoresis, magnetophoresis and laser techniques have been investigated for the past decades on their ability, mechanisms and limitations in modifying the skin microenvironment to promote drug diffusion and partition. Microwave, an electromagnetic wave characterized by frequencies range between 300MHz and 300GHz, has recently been reported as the potential skin permeation enhancer. Microwave has received a widespread application in food, engineering and medical sectors. Its potential use to facilitate transdermal drug transport is still in its infancy stage of evaluation. This review provides an overview and update on active methods utilizing electrical, magnetic, photomechanical and cavitational waves to overcome the skin barrier for transdermal drug administration with insights into mechanisms and future perspectives of the latest microwave technique described.

  9. Evidence for Health II: Overcoming barriers to using evidence in policy and practice.

    PubMed

    Andermann, Anne; Pang, Tikki; Newton, John N; Davis, Adrian; Panisset, Ulysses

    2016-03-14

    Even the highest quality evidence will have little impact unless it is incorporated into decision-making for health. It is therefore critical to overcome the many barriers to using evidence in decision-making, including (1) missing the window of opportunity, (2) knowledge gaps and uncertainty, (3) controversy, irrelevant and conflicting evidence, as well as (4) vested interests and conflicts of interest. While this is certainly not a comprehensive list, it covers a number of main themes discussed in the knowledge translation literature on this topic, and better understanding these barriers can help readers of the evidence to be more savvy knowledge users and help researchers overcome challenges to getting their evidence into practice. Thus, the first step in being able to use research evidence for improving population health is ensuring that the evidence is available at the right time and in the right format and language so that knowledge users can take the evidence into consideration alongside a multitude of other factors that also influence decision-making. The sheer volume of scientific publications makes it difficult to find the evidence that can actually help inform decisions for health. Policymakers, especially in low- and middle-income countries, require context-specific evidence to ensure local relevance. Knowledge synthesis and dissemination of policy-relevant local evidence is important, but it is still not enough. There are times when the interpretation of the evidence leads to various controversies and disagreements, which act as barriers to the uptake of evidence. Research evidence can also be influenced and misused for various aims and agendas. It is therefore important to ensure that any new evidence comes from reliable sources and is interpreted in light of the overall body of scientific literature. It is not enough to simply produce evidence, nor even to synthesize and package evidence into a more user-friendly format. Particularly at the policy

  10. Evidence for Health II: Overcoming barriers to using evidence in policy and practice.

    PubMed

    Andermann, Anne; Pang, Tikki; Newton, John N; Davis, Adrian; Panisset, Ulysses

    2016-01-01

    Even the highest quality evidence will have little impact unless it is incorporated into decision-making for health. It is therefore critical to overcome the many barriers to using evidence in decision-making, including (1) missing the window of opportunity, (2) knowledge gaps and uncertainty, (3) controversy, irrelevant and conflicting evidence, as well as (4) vested interests and conflicts of interest. While this is certainly not a comprehensive list, it covers a number of main themes discussed in the knowledge translation literature on this topic, and better understanding these barriers can help readers of the evidence to be more savvy knowledge users and help researchers overcome challenges to getting their evidence into practice. Thus, the first step in being able to use research evidence for improving population health is ensuring that the evidence is available at the right time and in the right format and language so that knowledge users can take the evidence into consideration alongside a multitude of other factors that also influence decision-making. The sheer volume of scientific publications makes it difficult to find the evidence that can actually help inform decisions for health. Policymakers, especially in low- and middle-income countries, require context-specific evidence to ensure local relevance. Knowledge synthesis and dissemination of policy-relevant local evidence is important, but it is still not enough. There are times when the interpretation of the evidence leads to various controversies and disagreements, which act as barriers to the uptake of evidence. Research evidence can also be influenced and misused for various aims and agendas. It is therefore important to ensure that any new evidence comes from reliable sources and is interpreted in light of the overall body of scientific literature. It is not enough to simply produce evidence, nor even to synthesize and package evidence into a more user-friendly format. Particularly at the policy

  11. Let's not contribute to disparities: the best methods for teaching clinicians how to overcome language barriers to health care.

    PubMed

    Diamond, Lisa C; Jacobs, Elizabeth A

    2010-05-01

    Clinicians should be educated about how language barriers contribute to disparities for patients with limited English proficiency (LEP). However, educators must avoid developing educational interventions that increase health disparities for LEP patients. For example, studies suggest that teaching "Medical Spanish" or related courses may actually contribute to health care disparities if clinicians begin using these non-English language skills inappropriately with patients. We discuss the risks and benefits of teaching specific cultural competence skills and make evidence-based recommendations for the teaching content and methods for educational interventions focused on overcoming language barriers in health care. At minimum, we suggest such interventions include: (1) the role of language barriers in health disparities, (2) means of overcoming language barriers, (3) how to work with interpreters, (4) identifying and fixing problems in interpreted encounters, and (5) appropriate and safe use of one's own limited non-English language skills.

  12. Overcoming Barriers to Eye Care: Patient Response to a Medical Social Worker in a Glaucoma Service.

    PubMed

    Fudemberg, Scott J; Amarasekera, Dilru C; Silverstein, Marlee H; Linder, Kathryn M; Heffner, Paul; Hark, Lisa A; Waisbourd, Michael

    2016-08-01

    This paper investigates the patient response to a medical social worker in a glaucoma clinic. The literature suggests that medical social workers are effective in a variety of health care settings, yet the efficacy of a medical social worker in an adult ophthalmic setting has not been studied. We present the results of a retrospective chart review of 50 patients with glaucoma referred to a medical social worker between January 5, 2015 and June 31, 2015 in an outpatient clinic of an urban eye hospital. Clinical and demographic data, as well as the data from a quality of care questionnaire, were collected for each patient. Patients rated their interaction with the medical social worker as highly positive (mean = 4.75, 5-point Likert scale), and nearly 90 % of patients expressed interest in future contact with the social worker. Additionally, most patients reported that the social worker resolved the issues they were facing (61.1 %), supported them in seeing their ophthalmologist (70.6 %), and helped them to manage their glaucoma (69.7 %). Reported barriers to glaucoma care were emotional distress; cost of office visits and medications; lack of medical insurance; transportation; poor medication adherence; impairment of daily activities; follow-up adherence; and language. As vision loss from glaucoma is irreversible, it is important to detect and treat patients at early stages of the disease. Therefore, it is imperative for patients to regularly visit their eye care providers and adhere to treatment and follow-up recommendations. This study suggests that a medical social worker could play a pivotal role in helping patients with glaucoma overcome barriers to treatment and facilitate disease management. PMID:26860278

  13. Overcoming the Barrier on Time Step Size in Multiscale Molecular Dynamics Simulation of Molecular Liquids.

    PubMed

    Omelyan, Igor P; Kovalenko, Andriy

    2012-01-10

    We propose and validate a new multiscale technique, the extrapolative isokinetic Nóse-Hoover chain orientational (EINO) motion multiple time step algorithm for rigid interaction site models of molecular liquids. It nontrivially combines the multiple time step decomposition operator method with a specific extrapolation of intermolecular interactions, complemented by an extended isokinetic Nosé-Hoover chain approach in the presence of translational and orientational degrees of freedom. The EINO algorithm obviates the limitations on time step size in molecular dynamics simulations. While the best existing multistep algorithms can advance from a 5 fs single step to a maximum 100 fs outer step, we show on the basis of molecular dynamics simulations of the TIP4P water that our EINO technique overcomes this barrier. Specifically, we have achieved giant time steps on the order of 500 fs up to 5 ps, which now become available in the study of equilibrium and conformational properties of molecular liquids without a loss of stability and accuracy.

  14. Translating Research to Practice: Overcoming Barriers to Implementing Effective Off-Campus Party Intervention. Issues in Prevention

    ERIC Educational Resources Information Center

    Higher Education Center for Alcohol, Drug Abuse, and Violence Prevention, 2012

    2012-01-01

    This issue of "Issues in Prevention" focuses on overcoming barriers in implementing effective off-campus party intervention. This issue contains the following articles: (1) Confronting the Problems Associated With Off-Campus Parties With Evidence-Based Strategies (John D. Clapp); (2) Overview of Research on Effective Off-Campus Party…

  15. Overcoming Relationship-Initiation Barriers: The Impact of a Computer-Dating System on Sex Role, Shyness, and Appearance Inhibitions.

    ERIC Educational Resources Information Center

    Scharlott, Bradford W.; Christ, William G.

    1995-01-01

    A survey of the users of an online computer-mediated matchmaking service showed that their communication patterns and objectives varied by their sex, shyness level, and appearance. Intrinsic aspects of this system helped some users overcome relationship-initiation barriers rooted in sex role, shyness, and appearance inhibitions. (Author)

  16. All Health Plans Need CLAMS: Culturally and Linguistically Appropriate Materials for Diverse Populations Can Overcome Language Barriers to Effective Treatment.

    ERIC Educational Resources Information Center

    Smith, Sandra; Gonzales, Virginia

    2000-01-01

    CLAMs are "Culturally and Linguistically Appropriate Materials" designed for diverse populations to help them overcome language barriers to effective treatment. The demographic shift underway in the United States is making the country more linguistically diverse. Health plans need to accommodate this shift, because without information patients…

  17. Overcoming the Fundamental Barrier Thickness Limits of Ferroelectric Tunnel Junctions through BaTiO3/SrTiO3 Composite Barriers.

    PubMed

    Wang, Lingfei; Cho, Myung Rae; Shin, Yeong Jae; Kim, Jeong Rae; Das, Saikat; Yoon, Jong-Gul; Chung, Jin-Seok; Noh, Tae Won

    2016-06-01

    Ferroelectric tunnel junctions (FTJs) have attracted increasing research interest as a promising candidate for nonvolatile memories. Recently, significant enhancements of tunneling electroresistance (TER) have been realized through modifications of electrode materials. However, direct control of the FTJ performance through modifying the tunneling barrier has not been adequately explored. Here, adding a new direction to FTJ research, we fabricated FTJs with BaTiO3 single barriers (SB-FTJs) and BaTiO3/SrTiO3 composite barriers (CB-FTJs) and reported a systematic study of FTJ performances by varying the barrier thicknesses and compositions. For the SB-FTJs, the TER is limited by pronounced leakage current for ultrathin barriers and extremely small tunneling current for thick barriers. For the CB-FTJs, the extra SrTiO3 barrier provides an additional degree of freedom to modulate the barrier potential and tunneling behavior. The resultant high tunability can be utilized to overcome the barrier thickness limits and enhance the overall CB-FTJ performances beyond those of SB-FTJ. Our results reveal a new paradigm to manipulate the FTJs through designing multilayer tunneling barriers with hybrid functionalities.

  18. Overcoming the Meter Barrier and The Formation of Systems with Tightly-packed Inner Planets (STIPs)

    NASA Astrophysics Data System (ADS)

    Boley, Aaron C.; Morris, Melissa A.; Ford, Eric B.

    2014-11-01

    The Kepler space mission has revealed numerous planetary types and systems, shaping our understanding of planet formation. Among the quickly-growing data is a subclass of multi-planet configurations referred to as Systems with Tightly-packed Inner Planets (STIPs). Their large abundance (>10% of stars) suggests that they are one of the principal outcomes of planet formation. The prototype STIP is Kepler-11, which hosts six known transiting planets, five of which have measured masses in the super-Earth and mini-Neptune regimes. The known planetary orbits in this system are spaced between a=0.09 and 0.47 AU, with small eccentricities and mutual inclinations. The lack of low-order mean motion resonances among planets in STIPs suggests that migration may have not played a dominant role in placing all of these planets on short orbital periods. While the formation of massive planetary systems on the hot side of the water ice line may be difficult to reconcile under the current paradigm of planet formation, we must explore whether many STIP planets formed by and large in situ. We discuss an overlooked mechanism that may allow the in situ formation of planetary systems on very short orbital periods. As solids spiral inward due to aerodynamic drag, they will enter disk regions that are characterized by high temperatures, densities, and pressures. High partial pressures of rock vapor can reduce net evaporation of incoming material, which could promote collisions between partially molten solids, allowing rapid growth and overcoming the classic meter barrier.

  19. Nanoparticles decorated with proteolytic enzymes, a promising strategy to overcome the mucus barrier.

    PubMed

    Pereira de Sousa, Irene; Cattoz, Beatrice; Wilcox, Matthew D; Griffiths, Peter C; Dalgliesh, Robert; Rogers, Sarah; Bernkop-Schnürch, Andreas

    2015-11-01

    The intestinal mucus gel layer represents a stumbling block for drug adsorption. This study is aimed to formulate a nanoparticulate system able to overcome this barrier by cleaving locally the glycoprotein substructures of the mucus. Mucolytic enzymes such as papain (PAP) and bromelain (BRO) were covalently conjugated to poly(acrylic acid) (PAA). Nanoparticles (NPs) were then formulated via ionic gelation method and characterized by particle size, zeta potential, enzyme content and enzymatic activity. The NPs permeation quantified by rotating tube studies was correlated with changes in the mucus gel layer structure determined by pulsed-gradient-spin-echo NMR (PGSE-NMR), small-angle neutron scattering (SANS) and spin-echo SANS (SESANS). PAP and BRO functionalized NPs had an average size in the range of 250 and 285 nm and a zeta potential that ranged between -6 and -5 mV. The enzyme content was 242 μg enzyme/mg for PAP modified NPs and 253 μg enzyme/mg for BRO modified NPs. The maintained enzymatic activity was 43% for PAP decorated NPs and 76% for BRO decorated NPs. The rotating tube technique revealed a better performance of BRO decorated NPs compared to PAA decorated NPs, with a 4.8-fold higher concentration of NPs in the inner slice of mucus. Addition of 0.5 wt% of enzyme functionalized NPs to 5 wt% intestinal mucin led to c.a. 2-fold increase in the mobility of the mucin as measured by PGSE-NMR indicative of a significant break-up of the structure of the mucin. SANS and SESANS measurements further revealed a change in structure of the intestinal mucus induced by the incorporation of the functionalized NPs mostly occurring at a length scale longer than 0.5 μm. Accordingly, BRO decorated NPs show higher potential than PAP functionalized NPs as mucus permeating drug delivery systems.

  20. Can Self-Prediction Overcome Barriers to Hepatitis B Vaccination? A Randomized Controlled Trial

    PubMed Central

    Cox, Anthony D.; Cox, Dena; Cyrier, Rosalie; Graham-Dotson, Yolanda; Zimet, Gregory D.

    2011-01-01

    Objective Hepatitis B virus (HBV) infection remains a serious public health problem, due in part to low vaccination rates among high-risk adults, many of whom decline vaccination because of barriers such as perceived inconvenience or discomfort. This study evaluates the efficacy of a self-prediction intervention to increase HBV vaccination rates among high-risk adults. Method Randomized controlled trial of 1175 adults recruited from three STD clinics in the United States over 28 months. Participants completed an audio-computer-assisted self-interview (A-CASI), which presented information about HBV infection and vaccination, and measured relevant beliefs, behaviors and demographics. Half of participants were assigned randomly to a "self-prediction" intervention, asking them to predict their future acceptance of HBV vaccination. The main outcome measure was subsequent vaccination behavior. Other measures included perceived barriers to HBV vaccination, measured prior to the intervention. Results There was a significant interaction between the intervention and vaccination barriers, indicating the effect of the intervention differed depending on perceived vaccination barriers. Among high-barriers patients, the intervention significantly increased vaccination acceptance. Among low-barrier patients, the intervention did not influence vaccination acceptance. Conclusions The self-prediction intervention significantly increased vaccination acceptance among "high-barriers" patients, who typically have very low vaccination rates. This brief intervention could be a useful tool in increasing vaccine uptake among high-barriers patients. PMID:21875205

  1. Energy management action plan: Developing a strategy for overcoming institutional barriers to municipal energy conservation

    SciTech Connect

    Not Available

    1992-12-31

    Energy offices working to improve efficiency of local government facilities face not only technical tasks, but institutional barriers, such as budget structures that do not reward efficiency, a low awareness of energy issues, and purchasing procedures based only on minimizing initial cost. The bureau, in working to remove such barriers in San Francisco, has identified 37 institutional barriers in areas such as operations & maintenance, purchasing, and facility design; these barriers were then reorganized into three groupings-- policy & attitudes, budget & incentives, and awareness & information-- and mapped. This map shows that the barriers mutually reinforce each other, and that a holistic approach is required for permanent change. The city`s recreation & parks department was used as a model department, and information about facility energy use was compiled into a departmental energy review. Staff interviews showed how barriers affect conservation. The bureau then generated ideas for projects to remove specific barriers and rated them according to potential impact and the resources required to implement them. Four of the six projects selected focused on maintenance staff: a cost- sharing lighting retrofit program, a boiler efficiency program, a departmental energy tracking system, and a budgetary incentive program for conservation. The other two projects are city-wide: promotion of a new term contract supplying energy-efficient light materials, and publication/distribution of ENERGY NEWS newsletter. A general methodology, the EMAP Strategy Guide, has been created to assist other energy offices in developing EMAPs.

  2. Principles of nanoparticle design for overcoming biological barriers to drug delivery

    PubMed Central

    Blanco, Elvin; Shen, Haifa; Ferrari, Mauro

    2016-01-01

    Biological barriers to drug transport prevent successful accumulation of nanotherapeutics specifically at diseased sites, limiting efficacious responses in disease processes ranging from cancer to inflammation. Although substantial research efforts have aimed to incorporate multiple functionalities and moieties within the overall nanoparticle design, many of these strategies fail to adequately address these barriers. Obstacles, such as nonspecific distribution and inadequate accumulation of therapeutics, remain formidable challenges to drug developers. A reimagining of conventional nanoparticles is needed to successfully negotiate these impediments to drug delivery. Site-specific delivery of therapeutics will remain a distant reality unless nanocarrier design takes into account the majority, if not all, of the biological barriers that a particle encounters upon intravenous administration. By successively addressing each of these barriers, innovative design features can be rationally incorporated that will create a new generation of nanotherapeutics, realizing a paradigmatic shift in nanoparticle-based drug delivery. PMID:26348965

  3. Tailored interventions to overcome identified barriers to change: effects on professional practice and health care outcomes

    PubMed Central

    Baker, Richard; Camosso-Stefinovic, Janette; Gillies, Clare; Shaw, Elizabeth J; Cheater, Francine; Flottorp, Signe; Robertson, Noelle

    2014-01-01

    Background In the previous version of this review, the effectiveness of interventions tailored to barriers to change was found to be uncertain. Objectives To assess the effectiveness of interventions tailored to address identified barriers to change on professional practice or patient outcomes. Search methods For this update, in addition to the EPOC Register and pending files, we searched the following databases without language restrictions, from inception until August 2007: MEDLINE, EMBASE, CINAHL, BNI and HMIC. We searched the National Research Register to November 2007. We undertook further searches to October 2009 to identify potentially eligible published or ongoing trials. Selection criteria Randomised controlled trials (RCTs) of interventions tailored to address prospectively identified barriers to change that reported objectively measured professional practice or healthcare outcomes in which at least one group received an intervention designed to address prospectively identified barriers to change. Data collection and analysis Two reviewers independently assessed quality and extracted data. We undertook quantitative and qualitative analyses. The quantitative analyses had two elements. We carried out a meta-regression to compare interventions tailored to address identified barriers to change with either no interventions or an intervention(s) not tailored to the barriers.We carried out heterogeneity analyses to investigate sources of differences in the effectiveness of interventions. These included the effects of: risk of bias, concealment of allocation, rigour of barrier analysis, use of theory, complexity of interventions, and the reported presence of administrative constraints. Main results We included 26 studies comparing an intervention tailored to address identified barriers to change to no intervention or an intervention(s) not tailored to the barriers. The effect sizes of these studies varied both across and within studies. Twelve studies provided

  4. Defining and overcoming barriers between Euro-American chaplains and African American families.

    PubMed

    Bradley, Joe

    2009-01-01

    This article describes various communication barriers between Euro-American chaplains and African American families which prevent effective spiritual care. These barriers include covert and deeply internalized racism, belief in false ideologies, persistent stereotyping, and being unaware of white privilege. Proposes potential solutions of acknowledging ones own race; becoming sensitive to the history and continuing oppression of Euro-Americans toward African Americans; building multicultural competence through education; and building equal-status relationships with African American individuals.

  5. 'We do the impossible': women overcoming barriers to cervical cancer screening in rural Honduras--a positive deviance analysis.

    PubMed

    Garrett, Jenna J; Barrington, Clare

    2013-01-01

    Cervical cancer is the leading cause of cancer death for women in Honduras, and sexual behaviour and low screening uptake are two major factors contributing to high rates of morbidity and mortality. A qualitative study was conducted to investigate barriers that prevent rural Honduran women from engaging in screening and ways that women overcome those barriers. This study examined examples of positive deviance, or individuals engaging in the uncommon but beneficial practise of screening. Amor por sí misma (self-love), and social support were identified as two constructs women employed to overcome barriers to screening. Participants defined self-love as the act of displaying care and concern for oneself and one's health and suggested that it compels women to participate in screening. Social support was defined as receiving tangible aid and advice from others that facilitated women's screening participation. Findings suggest that the concept of self-love could be used in future screening promotion efforts and that integrating social support would also be beneficial. Engaging men in sexual and reproductive health programming is suggested in order to ensure male partners offer social support for screening and to challenge the cultural, gender and sexual norms that place women at higher risk for cervical cancer.

  6. Ground-Source Heat Pumps. Overview of Market Status, Barriers to Adoption, and Options for Overcoming Barriers

    SciTech Connect

    Goetzler, William; Zogg, Robert; Lisle, Heather; Burgos, Javier

    2009-02-03

    February 2009 final report submitted to DOE by Navigant Consulting, Inc. This report summarizes the status of ground-source heat pump (GSHP) technology and market penetration globally, estimates the energy saving potential of GSHPs in the U.S., identifies key market barriers that are inhibiting wider market adoption of GSHPs, and recommends initiatives that can be implemented or facilitated by the DOE to accelerate market adoption.

  7. Overcoming Barriers for Displaced Homemakers in Nontraditional Occupations. A Manual of Strategies.

    ERIC Educational Resources Information Center

    Far West Lab. for Educational Research and Development, San Francisco, CA.

    This manual examines problems the displaced homemaker encounters on the job and offers strategies which vocational educators, counselors, and other service providers can suggest to nontraditional students for overcoming these problems. A brief overview of the displaced homemaker is provided and the term "nontraditional occupation" is defined. An…

  8. Overcoming the barrier of narrative adherence in conflicts through awareness of the psychological bias of naïve realism.

    PubMed

    Nasie, Meytal; Bar-Tal, Daniel; Pliskin, Ruthie; Nahhas, Eman; Halperin, Eran

    2014-11-01

    One significant socio-psychological barrier for peaceful resolution of conflicts is each party's adherence to its own collective narrative. We hypothesized that raising awareness to the psychological bias of naïve realism and its identification in oneself would provide a path to overcoming this barrier, thus increasing openness to the adversary's narrative. We conducted three experimental studies in the context of the Israeli-Palestinian conflict. Studies 1 and 2, conducted among Jewish Israelis and Palestinian Israelis, respectively, revealed that participants with hawkish political ideology reported greater openness to the adversary's narrative when they were made aware of naïve realism bias. Study 3 revealed that hawkish participants at the baseline adhered to the ingroup narrative and resisted the adversary's narrative more than dovish participants. They were also more able to identify the bias in themselves upon learning about it. This identification may explain why the manipulation led to bias correction only among hawkish participants.

  9. Overcoming Barriers to the Sexual Expression of Women with Developmental Disabilities.

    ERIC Educational Resources Information Center

    Stinson, Jennifer; Christian, LeeAnn; Dotson, Lori Ann

    2002-01-01

    This article discusses barriers to sexual fulfillment faced by women with developmental disabilities, including: access to gynecological healthcare, limited choices regarding reproductive issues, lack of sex education, and prevailing negative stereotypes that affect the way women are viewed by others and the way they view themselves.…

  10. Designing Caregiver-Implemented Shared-Reading Interventions to Overcome Implementation Barriers

    ERIC Educational Resources Information Center

    Justice, Laura M.; Logan, Jessica R.; Damschroder, Laura

    2015-01-01

    Purpose: This study presents an application of the theoretical domains framework (TDF; Michie et al., 2005), an integrative framework drawing on behavior-change theories, to speech-language pathology. Methods: A multistep procedure was used to identify barriers affecting caregivers' implementation of shared-reading interventions with their…

  11. At-Risk Students Defy the Odds: Overcoming Barriers to Educational Success.

    ERIC Educational Resources Information Center

    Aronson, Rosa

    The phenomenon of educational resilience in at-risk students involves complex questions and answers. Seven people were interviewed whose lives are chronicled in the context of surviving and achieving despite significant barriers to success in life. They encountered common hindrances arising from poverty, racial and ethnic identity, isolation,…

  12. Strategies for Overcoming Barriers to Training and Education for Canadians with Disabilities. Lessons in Learning

    ERIC Educational Resources Information Center

    Canadian Council on Learning, 2009

    2009-01-01

    If stronger skills and more education are key to greater labour force participation, then it is important to identify critical barriers to education and training for Canadians with disabilities. In 2008, the Canadian Council on Learning's Adult Learning Knowledge Centre funded a "Community Outreach Initiative for Learner's with Disabilities" that…

  13. Strategies for overcoming the blood-brain barrier for the treatment of brain metastases.

    PubMed

    Hu, Jethro; Kesari, Santosh

    2013-01-01

    The era of targeted therapy for cancer has been punctuated by some resounding successes, but with few exceptions, metastases to the brain remain frustratingly difficult to treat. It is increasingly apparent that old concerns regarding the ability of therapeutic agents to penetrate the blood-brain barrier have not been brushed aside by high-affinity small-molecule kinase inhibitors and monoclonal antibodies. Indeed, illustrative trends, such as the increasing incidence of brain metastases from HER2(+) breast cancer since the advent of trastuzumab therapy, have helped to solidify the concept of the CNS as a sanctuary site for cancer. With 200,000 patients diagnosed with brain metastases in the USA each year, the therapeutic challenge posed by the blood-brain barrier continues to be a big problem.

  14. Overcoming Barriers to the Market Access of Biosimilars in the European Union: The Case of Biosimilar Monoclonal Antibodies

    PubMed Central

    Moorkens, Evelien; Jonker-Exler, Clara; Huys, Isabelle; Declerck, Paul; Simoens, Steven; Vulto, Arnold G.

    2016-01-01

    Background: In 2014, six of the top ten blockbuster medicines were monoclonal antibodies. This multibillion-dollar market with expiring patents is the main driver for the development of biosimilar mAbs. With the ever-increasing cost of healthcare and the economic pressure to reduce or sustain healthcare expenses, biosimilars could be instrumental in reducing costs for medication and increasing patient access to treatment. Objectives: The aim of this study is to identify and describe the barriers to market access of biosimilar mAbs in the European Union and to analyze how these barriers could be overcome. Methods: A narrative literature review was carried out using the databases PubMed, Embase, and EconLit. Studies were published in English or Dutch. Additionally, the reference list of the articles was checked for relevant studies. Articles and conference papers known to the authors were included as well. Articles were also identified by searching on the website of the Generics and Biosimilars Initiative (GaBI) journal. Results: Six barriers were identified based on available literature: The manufacturing process, the regulatory process, intellectual property rights, lack of incentive, the impossibility of substitution, and the innovator's reach. These six barriers are presented as a possible framework to study the market access of biosimilar mAbs. Based on the literature search, recommendations can be made to overcome these barriers: (i) invest initially in advanced production processes with the help of single-use technology, experience or outsourcing (ii) gain experience with the regulatory process and establish alignment between stakeholders (iii) limit patent litigation, eliminate evergreening benefits, build out further the unitary patent and unified patent litigation system within the EU (iv) create demand-side policies, disseminate objective information (v) change attitude toward biosimilar switching/substitution, starting with physician, and patient

  15. Overcoming barriers to the mobilisation of patients in an intensive care unit.

    PubMed

    Dafoe, S; Chapman, M J; Edwards, S; Stiller, K

    2015-11-01

    We conducted a quality improvement project aimed at increasing the frequency of mobilisation in our ICU. We designed a four-part quality improvement project comprising: an audit documenting the baseline frequency of mobilisation; a staff survey evaluating perceptions of the barriers to mobilisation; identification of barriers that were amenable to change and implementation of strategies to address these; and a follow-up audit to determine their effectiveness. The setting was a tertiary care, urban, public hospital ICU in South Australia. All patients admitted to the ICU during the two audit periods were included in the audits, while all permanent/semi-permanent ICU staff were eligible for inclusion in the staff survey. We found that patient- and institution-related factors had the greatest impact on the mobilisation of patients in our ICU. Barriers identified as being amenable to change included insufficient staff education about the benefits of mobilisation, poor interdisciplinary communication and lack of leadership regarding mobilisation. Various strategies were implemented to address these barriers over a three-month period. Multivariable analyses showed that three out of four mobility outcomes did not significantly change between the baseline and follow-up audits, with a significant difference in favour of the baseline audit found for the fourth mobility outcome (maximum level of mobility). We concluded that implementing relatively simple measures to improve staff education, interdisciplinary communication and leadership regarding early progressive mobilisation was ineffective at improving mobility outcomes for patients in a large tertiary-level Australian ICU. Other strategies, such as changing sedation practices and/or increasing staffing, may be required to improve mobility outcomes of these patients. PMID:26603796

  16. Overcoming the Barrier Treatment of Ichthyosis: A Combination-therapy Approach.

    PubMed

    Bellew, Susun; Del Rosso, James Q

    2010-07-01

    Ichthyosis vulgaris is an inherited disorder of keratinization that results in asteatotic scales on extensor surfaces of the arm, legs, and trunk. A combination-therapy approach with a physiological lipid-based barrier repair topical emulsion and ammonium lactate 12% lotion applied topically was shown to be effective at four-week follow up without any untoward side effects. This combination therapy addresses the importance of caring for both the corneocytes ("bricks") and the intercellular lipid bilayer ("mortar") for optimal benefit.

  17. Overcoming barriers to the mobilisation of patients in an intensive care unit.

    PubMed

    Dafoe, S; Chapman, M J; Edwards, S; Stiller, K

    2015-11-01

    We conducted a quality improvement project aimed at increasing the frequency of mobilisation in our ICU. We designed a four-part quality improvement project comprising: an audit documenting the baseline frequency of mobilisation; a staff survey evaluating perceptions of the barriers to mobilisation; identification of barriers that were amenable to change and implementation of strategies to address these; and a follow-up audit to determine their effectiveness. The setting was a tertiary care, urban, public hospital ICU in South Australia. All patients admitted to the ICU during the two audit periods were included in the audits, while all permanent/semi-permanent ICU staff were eligible for inclusion in the staff survey. We found that patient- and institution-related factors had the greatest impact on the mobilisation of patients in our ICU. Barriers identified as being amenable to change included insufficient staff education about the benefits of mobilisation, poor interdisciplinary communication and lack of leadership regarding mobilisation. Various strategies were implemented to address these barriers over a three-month period. Multivariable analyses showed that three out of four mobility outcomes did not significantly change between the baseline and follow-up audits, with a significant difference in favour of the baseline audit found for the fourth mobility outcome (maximum level of mobility). We concluded that implementing relatively simple measures to improve staff education, interdisciplinary communication and leadership regarding early progressive mobilisation was ineffective at improving mobility outcomes for patients in a large tertiary-level Australian ICU. Other strategies, such as changing sedation practices and/or increasing staffing, may be required to improve mobility outcomes of these patients.

  18. Overcoming barriers in care for the dying: Theoretical analysis of an innovative program model.

    PubMed

    Wallace, Cara L

    2016-08-01

    This article explores barriers to end-of-life (EOL) care (including development of a death denying culture, ongoing perceptions about EOL care, poor communication, delayed access, and benefit restrictions) through the theoretical lens of symbolic interactionism (SI), and applies general systems theory (GST) to a promising practice model appropriate for addressing these barriers. The Compassionate Care program is a practice model designed to bridge gaps in care for the dying and is one example of a program offering concurrent care, a recent focus of evaluation though the Affordable Care Act. Concurrent care involves offering curative care alongside palliative or hospice care. Additionally, the program offers comprehensive case management and online resources to enrollees in a national health plan (Spettell et al., 2009).SI and GST are compatible and interrelated theories that provide a relevant picture of barriers to end-of-life care and a practice model that might evoke change among multiple levels of systems. These theories promote insight into current challenges in EOL care, as well as point to areas of needed research and interventions to address them. The article concludes with implications for policy and practice, and discusses the important role of social work in impacting change within EOL care.

  19. Zelda overcomes the high intrinsic nucleosome barrier at enhancers during Drosophila zygotic genome activation.

    PubMed

    Sun, Yujia; Nien, Chung-Yi; Chen, Kai; Liu, Hsiao-Yun; Johnston, Jeff; Zeitlinger, Julia; Rushlow, Christine

    2015-11-01

    The Drosophila genome activator Vielfaltig (Vfl), also known as Zelda (Zld), is thought to prime enhancers for activation by patterning transcription factors (TFs). Such priming is accompanied by increased chromatin accessibility, but the mechanisms by which this occurs are poorly understood. Here, we analyze the effect of Zld on genome-wide nucleosome occupancy and binding of the patterning TF Dorsal (Dl). Our results show that early enhancers are characterized by an intrinsically high nucleosome barrier. Zld tackles this nucleosome barrier through local depletion of nucleosomes with the effect being dependent on the number and position of Zld motifs. Without Zld, Dl binding decreases at enhancers and redistributes to open regions devoid of enhancer activity. We propose that Zld primes enhancers by lowering the high nucleosome barrier just enough to assist TFs in accessing their binding motifs and promoting spatially controlled enhancer activation if the right patterning TFs are present. We envision that genome activators in general will utilize this mechanism to activate the zygotic genome in a robust and precise manner.

  20. Pathogen population bottlenecks and adaptive landscapes: overcoming the barriers to disease emergence.

    PubMed

    Geoghegan, Jemma L; Senior, Alistair M; Holmes, Edward C

    2016-08-31

    Emerging diseases are a major challenge to public health. Revealing the evolutionary processes that allow novel pathogens to adapt to new hosts, also the potential barriers to host adaptation, is central to understanding the drivers of disease emergence. In particular, it is unclear how the genetics and ecology of pathogens interact to shape the likelihood of successful cross-species transmission. To better understand the determinants of host adaptation and emergence, we modelled key aspects of pathogen evolutionary dynamics at both intra- and inter-host scales, using parameter values similar to those observed in influenza virus. We considered the possibility of acquiring the necessary host adaptive mutations both before ('off-the-shelf' emergence) and after ('tailor-made' emergence) a virus is transmitted from a donor to a new recipient species. Under both scenarios, population bottlenecks at inter-host transmission act as a major barrier to host adaptation, greatly limiting the number of adaptive mutations that are able to cross the species barrier. In addition, virus emergence is hindered if the fitness valley between the donor and recipient hosts is either too steep or too shallow. Overall, our results reveal where in evolutionary parameter space a virus could adapt to and become transmissible in a new species. PMID:27581875

  1. Overcoming barriers in care for the dying: Theoretical analysis of an innovative program model.

    PubMed

    Wallace, Cara L

    2016-08-01

    This article explores barriers to end-of-life (EOL) care (including development of a death denying culture, ongoing perceptions about EOL care, poor communication, delayed access, and benefit restrictions) through the theoretical lens of symbolic interactionism (SI), and applies general systems theory (GST) to a promising practice model appropriate for addressing these barriers. The Compassionate Care program is a practice model designed to bridge gaps in care for the dying and is one example of a program offering concurrent care, a recent focus of evaluation though the Affordable Care Act. Concurrent care involves offering curative care alongside palliative or hospice care. Additionally, the program offers comprehensive case management and online resources to enrollees in a national health plan (Spettell et al., 2009).SI and GST are compatible and interrelated theories that provide a relevant picture of barriers to end-of-life care and a practice model that might evoke change among multiple levels of systems. These theories promote insight into current challenges in EOL care, as well as point to areas of needed research and interventions to address them. The article concludes with implications for policy and practice, and discusses the important role of social work in impacting change within EOL care. PMID:27332743

  2. Enhanced Oral Delivery of Protein Drugs Using Zwitterion-Functionalized Nanoparticles to Overcome both the Diffusion and Absorption Barriers.

    PubMed

    Shan, Wei; Zhu, Xi; Tao, Wei; Cui, Yi; Liu, Min; Wu, Lei; Li, Lian; Zheng, Yaxian; Huang, Yuan

    2016-09-28

    Oral delivery of protein drugs based on nanoparticulate delivery system requires permeation of the nanoparticles through the mucus layer and subsequent absorption via epithelial cells. However, overcoming these two barriers requires very different or even contradictory surface properties of the nanocarriers, which greatly limits the oral bioavailability of macromolecular drugs. Here we report a simple zwitterions-based nanoparticle (NP) delivery platform, which showed a great potency in simultaneously overcoming both the mucus and epithelium barriers. The dense and hydrophilic coating of zwitterions endows the NPs with excellent mucus penetrating ability. Moreover, the zwitterions-based NPs also possessed excellent affinity with epithelial cells, which significantly improved (4.5-fold) the cellular uptake of DLPC NPs, compared to PEGylated NPs. Our results also indicated that this affinity was due to the interaction between zwitterions and the cell surface transporter PEPT1. Moreover, the developed NPs loaded with insulin could induce a prominent hypoglycemic response in diabetic rats following oral administration. These results suggest that zwitterions-based NPs might provide a new perspective for oral delivery of protein therapeutics.

  3. AccessAbility: Overcoming Information Barriers. Proceedings from the 1987 Spring Meeting of the Nebraska Library Association, College and University Section (Omaha, Nebraska, May 29, 1987).

    ERIC Educational Resources Information Center

    Kacena, Barbara J., Ed.

    Various aspects of the theme, "AccessAbility: Overcoming Information Barriers," are considered in the conference papers collected in this document. They include: (1) "The Library Image: A Barrier to Accessibility" (Janice S. Boyer); (2) "The Educationally Disadvantaged Student: How Can the Library Help?" (Michael Poma and Richard Jehlik); (3)…

  4. [Overcoming language barriers with telephone interpreters: first experiences at a German children's hospital].

    PubMed

    Langer, Thorsten; Wirth, Stefan

    2014-01-01

    Language barriers in the care for patients with limited German language proficiency contribute to impaired quality of care, more frequent medical errors and decreased patient satisfaction. However, professional interpreters are not systematically used in Germany. We conducted a pilot study in a German paediatric hospital to explore the demand for an interpreter by conducting a survey among parents and to test the use of telephone interpreters. Eight percent of the respondents said they were interested in interpreter support. All physicians and parents using a telephone interpreter were very satisfied with the quality and the organisation of the service.

  5. "Take your own path": minority leaders encountering and overcoming barriers in cultural community centers.

    PubMed

    Flores, Kevin Lynn; Matkin, Gina Sue

    2014-01-01

    Minority leaders face workplace issues not experienced by white leaders including lack of support, discrimination, racism, and stereotyping. The purpose of this study was to explore how racial/ethnic minority leaders encountered and overcame barriers as leaders of cultural community centers. Three racial/ethnic minority executive directors of cultural community centers located in a Midwestern city were interviewed and their responses were hand-coded to develop themes. Six themes emerged from this process: finding "inspiration", "developing thick skin", "stereotypes", "damage from within", "take your path", and "hope". Their stories help us understand the complexities of inter-racial relations in the workplace.

  6. Overcoming barriers to addressing education problems with research design: a panel discussion.

    PubMed

    Yarris, Lalena M; Gruppen, Larry D; Hamstra, Stanley J; Anders Ericsson, K; Cook, David A

    2012-12-01

    A plenary panel session at the 2012 Academic Emergency Medicine consensus conference "Education Research in Emergency Medicine: Opportunities, Challenges, and Strategies for Success" discussed barriers educators face in imagining, designing, and implementing studies to address educational challenges. This proceedings article presents a general approach to getting started in education research. Four examples of studies from the medical education literature that illustrate a distinct way to approach specific research questions are discussed. The study designs used are applicable to a variety of education research problems in emergency medicine (EM). Potential applications of studies are discussed, as well as effects and lessons learned.

  7. OVERCOMING THE METER BARRIER AND THE FORMATION OF SYSTEMS WITH TIGHTLY PACKED INNER PLANETS (STIPs)

    SciTech Connect

    Boley, A. C.; Morris, M. A.; Ford, E. B.

    2014-09-10

    We present a solution to the long outstanding meter barrier problem in planet formation theory. As solids spiral inward due to aerodynamic drag, they will enter disk regions that are characterized by high temperatures, densities, and pressures. High partial pressures of rock vapor can suppress solid evaporation, and promote collisions between partially molten solids, allowing rapid growth. This process should be ubiquitous in planet-forming disks, which may be evidenced by the abundant class of Systems with Tightly packed Inner Planets discovered by the NASA Kepler Mission.

  8. Behavioral training and AIDS risk reduction: overcoming barriers to condom use.

    PubMed

    Weisse, C S; Turbiasz, A A; Whitney, D J

    1995-02-01

    To assess the short- and long-term effects of an AIDS-prevention workshop on undergraduates' attitudes about condom use and AIDS, 31 participants and 31 controls were studied immediately after training sessions as well as three months later. The workshop was aimed at reducing embarrassment to purchase condoms, encouraging positive attitudes about condoms, and promoting knowledge about AIDS. To help students overcome their embarrassment over condom purchases, a behavioral intervention was included allowing students to make condom purchases at nearby drug stores. Results revealed that participants reported less embarrassment over condom purchases after training sessions and that this effect became even stronger over time. Knowledge about AIDS and positive attitudes about condoms also increased immediately after the workshop, but these changes did not persist. Results suggest that AIDS prevention workshops may lead to transient changes unless a specific skill (i.e., condom purchasing) is targeted via behavioral training.

  9. Overcoming barriers to health-care access: A qualitative study among African migrants in Guangzhou, China.

    PubMed

    Lin, Lavinia; Brown, Katherine B; Hall, Brian J; Yu, Fan; Yang, Jingqi; Wang, Jason; Schrock, Joshua M; Bodomo, Adams B; Yang, Ligang; Yang, Bin; Nehl, Eric J; Tucker, Joseph D; Wong, Frank Y

    2016-10-01

    Guangzhou is China's third most populous city, and the region's burgeoning manufacturing economy has attracted many young African businessmen and entrepreneurs to the city. The aims of this study were to examine strategies that African migrants in Guangzhou have adopted in response to health-care barriers, and explore their perceptions of how to address their needs. Twenty-five semi-structured interviews and two focus groups were conducted among African migrants residing in Guangzhou, China. Facing multiple barriers to care, African migrants have adopted a number of suboptimal and unsustainable approaches to access health care. These included: using their Chinese friends or partners as interpreters, self-medicating, using personal connections to medical doctors, and travelling to home countries or countries that offer English-speaking doctors for health care. Health-care providers and health organisations in Guangzhou have not yet acquired sufficient cultural competence to address the needs of African migrants residing in the city. Introducing linguistically and culturally competent health-care services in communities concentrated with African migrants may better serve the population. With the growing international migration to China, it is essential to develop sustainable approaches to improving health-care access for international migrants, particularly those who are marginalised.

  10. Overcoming Workplace Barriers: A Focus Group Study Exploring African American Mothers' Needs for Workplace Breastfeeding Support

    PubMed Central

    Johnson, Angela Marie; Kirk, Rosalind; Muzik, Maria

    2015-01-01

    Background Persistent racial disparities in breastfeeding show that African American women breastfeed at the lowest rates. Return to work is a critical breastfeeding barrier for African American women who return to work sooner than other ethnic groups and more often encounter unsupportive work environments. They also face psychosocial burdens that make breastfeeding at work uniquely challenging. Participants share personal struggles with combining paid employment and breastfeeding and suggest workplace and personal support strategies that they believe will help continue breastfeeding after a return to work. Objective To explore current perspectives on ways to support African American mothers' workplace breastfeeding behavior. Methods Pregnant African American women (n = 8), African American mothers of infants (n = 21), and lactation support providers (n = 9) participated in 1 of 6 focus groups in the Greater Detroit area. Each focus group audiotape was transcribed verbatim. Thematic analysis was used to inductively analyze focus group transcripts and field notes. Focus groups explored thoughts, perceptions, and behavior on interventions to support African American women's breastfeeding. Results Participants indicate that they generally believed breastfeeding was a healthy option for the baby; however, paid employment is a critical barrier to successful breastfeeding for which mothers receive little help. Participants felt breastfeeding interventions that support working African American mothers should include education and training for health care professionals, regulation and enforcement of workplace breastfeeding support policies, and support from peers who act as breastfeeding role models. Conclusion Culturally appropriate interventions are needed to support breastfeeding among working African American women. PMID:25714345

  11. Overcoming barriers to health-care access: A qualitative study among African migrants in Guangzhou, China.

    PubMed

    Lin, Lavinia; Brown, Katherine B; Hall, Brian J; Yu, Fan; Yang, Jingqi; Wang, Jason; Schrock, Joshua M; Bodomo, Adams B; Yang, Ligang; Yang, Bin; Nehl, Eric J; Tucker, Joseph D; Wong, Frank Y

    2016-10-01

    Guangzhou is China's third most populous city, and the region's burgeoning manufacturing economy has attracted many young African businessmen and entrepreneurs to the city. The aims of this study were to examine strategies that African migrants in Guangzhou have adopted in response to health-care barriers, and explore their perceptions of how to address their needs. Twenty-five semi-structured interviews and two focus groups were conducted among African migrants residing in Guangzhou, China. Facing multiple barriers to care, African migrants have adopted a number of suboptimal and unsustainable approaches to access health care. These included: using their Chinese friends or partners as interpreters, self-medicating, using personal connections to medical doctors, and travelling to home countries or countries that offer English-speaking doctors for health care. Health-care providers and health organisations in Guangzhou have not yet acquired sufficient cultural competence to address the needs of African migrants residing in the city. Introducing linguistically and culturally competent health-care services in communities concentrated with African migrants may better serve the population. With the growing international migration to China, it is essential to develop sustainable approaches to improving health-care access for international migrants, particularly those who are marginalised. PMID:26400191

  12. Autism and Overcoming Job Barriers: Comparing Job-Related Barriers and Possible Solutions in and outside of Autism-Specific Employment.

    PubMed

    Lorenz, Timo; Frischling, Cora; Cuadros, Raphael; Heinitz, Kathrin

    2016-01-01

    The aim of this study was to discover how individuals with autism succeed in entering the job market. We therefore sought to identify expected and occurred barriers, keeping them from taking up and staying in employment as well as to identify the solutions used to overcome these barriers. Sixty-six employed individuals with autism--17 of them with autism-specific employment--participated in an online survey. Results showed a variety of possible barriers. Individuals in autism-specific employment named formality problems--problems with organizational and practical process-related aspects of the job entry--most frequently while individuals in non-autism-specific employment mentioned social problems--obstacles concerning communication and human interaction--most. In terms of solutions, both groups used their own resources as much as external help, but differed in their specific strategies. In addition, correlations of an autism-specific employment with general and occupational self-efficacy as well as life and job satisfaction were examined. Possible implications of the results are discussed with regard to problem solving behavior and the use of strengths. PMID:26766183

  13. Autism and Overcoming Job Barriers: Comparing Job-Related Barriers and Possible Solutions in and outside of Autism-Specific Employment.

    PubMed

    Lorenz, Timo; Frischling, Cora; Cuadros, Raphael; Heinitz, Kathrin

    2016-01-01

    The aim of this study was to discover how individuals with autism succeed in entering the job market. We therefore sought to identify expected and occurred barriers, keeping them from taking up and staying in employment as well as to identify the solutions used to overcome these barriers. Sixty-six employed individuals with autism--17 of them with autism-specific employment--participated in an online survey. Results showed a variety of possible barriers. Individuals in autism-specific employment named formality problems--problems with organizational and practical process-related aspects of the job entry--most frequently while individuals in non-autism-specific employment mentioned social problems--obstacles concerning communication and human interaction--most. In terms of solutions, both groups used their own resources as much as external help, but differed in their specific strategies. In addition, correlations of an autism-specific employment with general and occupational self-efficacy as well as life and job satisfaction were examined. Possible implications of the results are discussed with regard to problem solving behavior and the use of strengths.

  14. Autism and Overcoming Job Barriers: Comparing Job-Related Barriers and Possible Solutions in and outside of Autism-Specific Employment

    PubMed Central

    Lorenz, Timo; Frischling, Cora; Cuadros, Raphael; Heinitz, Kathrin

    2016-01-01

    The aim of this study was to discover how individuals with autism succeed in entering the job market. We therefore sought to identify expected and occurred barriers, keeping them from taking up and staying in employment as well as to identify the solutions used to overcome these barriers. Sixty-six employed individuals with autism–17 of them with autism-specific employment–participated in an online survey. Results showed a variety of possible barriers. Individuals in autism-specific employment named formality problems–problems with organizational and practical process-related aspects of the job entry–most frequently while individuals in non-autism-specific employment mentioned social problems–obstacles concerning communication and human interaction–most. In terms of solutions, both groups used their own resources as much as external help, but differed in their specific strategies. In addition, correlations of an autism-specific employment with general and occupational self-efficacy as well as life and job satisfaction were examined. Possible implications of the results are discussed with regard to problem solving behavior and the use of strengths. PMID:26766183

  15. Learning from the best: Overcoming barriers to reforms-based elementary science teaching

    NASA Astrophysics Data System (ADS)

    Banchi, Heather May

    This study explored the characteristics of elementary science teachers who employ reforms-based practices. Particular attention was paid to the consistency of teachers' practices and their beliefs, the impact of professional development experiences on practices, and how teachers mitigated barriers to reforms-based instruction. Understanding how successful elementary science teachers develop fills a gap in the science reforms literature. Participants included 7 upper elementary science teachers from six different schools. All schools were located within two suburban school districts in the south-Atlantic United States and data was collected during the spring of 2008. Data collection included use of the Reformed Teaching Observation Protocol (RTOP) to evaluate the level of reforms-based instruction, as well as 35 hours of classroom observation field notes and 21 hours of audio-taped teacher interviews. The variety of data sources allowed for triangulation of evidence. The RTOP was analyzed using descriptive statistics and classroom observations and interview data were analyzed using Erickson's (1986) guidelines for analytic induction. Findings indicated (a) reforms-based elementary science teaching was attainable, (b) beliefs and practices were consistent and both reflected reforms-based philosophies and practices, (c) formal professional development experiences were limited and did not foster reforms-based practices, (d) informal professional development pursued by teachers had a positive impact on practices, (e) barriers to reforms-based instruction were present but mitigated by strong beliefs and practical strategies like curriculum integration. These findings suggest that there are common, salient characteristics of reforms-based teachers' beliefs, practices, and professional development experiences. These commonalities contribute to an understanding of how reforms-based teachers develop, and inform efforts to move all elementary teachers in the direction of

  16. Exploring ways to overcome barriers to mammography uptake and retention among South Asian immigrant women.

    PubMed

    Ahmad, Farah; Jandu, Barinder; Albagli, Andrea; Angus, Jan E; Ginsburg, Ophira

    2013-01-01

    South Asians comprise one of the fastest growing immigrant groups in North America. Evidence indicates that South Asian (SA) immigrant women are vulnerable to low rates of breast cancer screening. Yet, there is a dearth of knowledge pertaining to socioculturally tailored strategies to guide the uptake of screening mammography in the SA community. In 2010, the authors conducted semi-structured focus groups (FG) to elicit perspectives of health and social service professionals on possible solutions to barriers identified by SA immigrant women in a recent study conducted in the Greater Toronto Area. Thirty-five health and social services staff members participated in five FG. The discussions were audio taped and detailed field notes were taken. All collected data were transcribed verbatim and thematic analysis was conducted using techniques of constant comparison within and across the group discussions. Three dominant themes were identified: (i) 'Target and Tailor' focused on awareness raising through multiple direct and indirect modes or approaches with underlying shared processes of involving men and the whole family, use of first language and learning from peers; (ii) 'Enhancing Access to Services' included a focus on 'adding ancillary services' and 'reinforcement of existing services' including expansion to a one-stop model; and (iii) 'Meta-Characteristics' centred on providing 'multi-pronged' approaches to reach the community, and 'sustainability' of initiatives by addressing structural barriers of adequate funding, healthcare provider mix, inter-sectoral collaboration and community voice. The findings simultaneously shed light on the grassroot practical strategies and the system level changes to develop efficient programmes for the uptake of mammography among SA immigrant women. The parallel focus on the 'Target and Tailor' and 'Enhancing Access to Services' calls for co-ordination at the policy level so that multiple sectors work jointly to streamline resources

  17. Sustainable fuel, food, fertilizer and ecosystems through a global artificial photosynthetic system: overcoming anticompetitive barriers.

    PubMed

    Bruce, Alex; Faunce, Thomas

    2015-06-01

    This article discusses challenges that artificial photosynthetic (AP) systems will face when entering and competing in a global market characterized by established fossil fuel technology. It provides a perspective on the neoliberal principles underpinning much policy entrenching such environmentally destructive technology and outlines how competition law could aid overcoming these hurdles for AP development. In particular, it critiques the potential for competition law to promote a global AP initiative with greater emphasis on atmospheric carbon dioxide and nitrogen fixation (as well as solar-driven water splitting) to produce an equitable, globally distributed source of human food, fertilizer and biosphere sustainability, as well as hydrogen-based fuel. Some relevant strategies of competition law evaluated in this context include greater citizen-consumer involvement in shaping market values, legal requirements to factor services from the natural environment (i.e. provision of clean air, water, soil pollution degradation) into corporate costs, reform of corporate taxation and requirements to balance maximization of shareholder profit with contribution to a nominated public good, a global financial transactions tax, as well as prohibiting horizontal cartels, vertical agreements and unilateral misuse of market power. PMID:26052427

  18. Mucosal Vaccination Overcomes the Barrier to Recombinant Vaccinia Immunization Caused by Preexisting Poxvirus Immunity

    NASA Astrophysics Data System (ADS)

    Belyakov, Igor M.; Moss, Bernard; Strober, Warren; Berzofsky, Jay A.

    1999-04-01

    Overcoming preexisting immunity to vaccinia virus in the adult population is a key requirement for development of otherwise potent recombinant vaccinia vaccines. Based on our observation that s.c. immunization with vaccinia induces cellular and antibody immunity to vaccinia only in systemic lymphoid tissue and not in mucosal sites, we hypothesized that the mucosal immune system remains naive to vaccinia and therefore amenable to immunization with recombinant vaccinia vectors despite earlier vaccinia exposure. We show that mucosal immunization of vaccinia-immune BALB/c mice with recombinant vaccinia expressing HIV gp160 induced specific serum antibody and strong HIV-specific cytotoxic T lymphocyte responses. These responses occurred not only in mucosal but also in systemic lymphoid tissue, whereas systemic immunization was ineffective under these circumstances. In this context, intrarectal immunization was more effective than intranasal immunization. Boosting with a second dose of recombinant vaccinia was also more effective via the mucosal route. The systemic HIV-specific cytotoxic T lymphocyte response was enhanced by coadministration of IL-12 at the mucosal site. These results also demonstrate the independent compartmentalization of the mucosal versus systemic immune systems and the asymmetric trafficking of lymphocytes between them. This approach to circumvent previous vaccinia immunity may be useful for induction of protective immunity against infectious diseases and cancer in the sizable populations with preexisting immunity to vaccinia from smallpox vaccination.

  19. Sustainable fuel, food, fertilizer and ecosystems through a global artificial photosynthetic system: overcoming anticompetitive barriers

    PubMed Central

    Bruce, Alex; Faunce, Thomas

    2015-01-01

    This article discusses challenges that artificial photosynthetic (AP) systems will face when entering and competing in a global market characterized by established fossil fuel technology. It provides a perspective on the neoliberal principles underpinning much policy entrenching such environmentally destructive technology and outlines how competition law could aid overcoming these hurdles for AP development. In particular, it critiques the potential for competition law to promote a global AP initiative with greater emphasis on atmospheric carbon dioxide and nitrogen fixation (as well as solar-driven water splitting) to produce an equitable, globally distributed source of human food, fertilizer and biosphere sustainability, as well as hydrogen-based fuel. Some relevant strategies of competition law evaluated in this context include greater citizen–consumer involvement in shaping market values, legal requirements to factor services from the natural environment (i.e. provision of clean air, water, soil pollution degradation) into corporate costs, reform of corporate taxation and requirements to balance maximization of shareholder profit with contribution to a nominated public good, a global financial transactions tax, as well as prohibiting horizontal cartels, vertical agreements and unilateral misuse of market power. PMID:26052427

  20. Sustainable fuel, food, fertilizer and ecosystems through a global artificial photosynthetic system: overcoming anticompetitive barriers.

    PubMed

    Bruce, Alex; Faunce, Thomas

    2015-06-01

    This article discusses challenges that artificial photosynthetic (AP) systems will face when entering and competing in a global market characterized by established fossil fuel technology. It provides a perspective on the neoliberal principles underpinning much policy entrenching such environmentally destructive technology and outlines how competition law could aid overcoming these hurdles for AP development. In particular, it critiques the potential for competition law to promote a global AP initiative with greater emphasis on atmospheric carbon dioxide and nitrogen fixation (as well as solar-driven water splitting) to produce an equitable, globally distributed source of human food, fertilizer and biosphere sustainability, as well as hydrogen-based fuel. Some relevant strategies of competition law evaluated in this context include greater citizen-consumer involvement in shaping market values, legal requirements to factor services from the natural environment (i.e. provision of clean air, water, soil pollution degradation) into corporate costs, reform of corporate taxation and requirements to balance maximization of shareholder profit with contribution to a nominated public good, a global financial transactions tax, as well as prohibiting horizontal cartels, vertical agreements and unilateral misuse of market power.

  1. Research dedicated to children: SwissPedNet with its international links overcomes key barriers to proper research in paediatrics.

    PubMed

    Wenger, Pascale; Frey, Urs; Nadal, David

    2014-01-01

    Conducting clinical studies in the paediatric population is complex and difficult. Paediatricians deal with a vulnerable population, which primarily needs protection and where patient numbers are always low. In addition, the pharmaceutical industry often demonstrates lack of interest due to the small and non-rewarding market. Public awareness for the need of paediatric research is likewise limited. This results in lack of funding for academic studies. In Switzerland, there is a new initiative that strives to overcome the given barriers and hurdles. SwissPedNet is still in a start-up phase, but it is now ready for all collaborations of interest and keen to work together with all stakeholders on the medical progress and improvement of paediatric clinical research with the overall goal of implementing evidence-based medicine for our children (www.swisspednet.ch).

  2. Obtaining family consent for participation in Alzheimer's research in a Cuban-American population: strategies to overcome the barriers.

    PubMed

    Williams, C L; Tappen, R; Buscemi, C; Rivera, R; Lezcano, J

    2001-01-01

    Cultural values and beliefs affect family attitudes toward participation in research. Significant resistance to allowing their elders with dementia to participate in clinical research was encountered in Cuban-American families. These families expressed concern about disturbing the elder's comfort (tranquilidad) and solitude (soledad). Furthermore, most believed that intervention would be futile. Feelings of guilt associated with nursing home placement may have been exacerbated by the suggestion that active intervention could be effective. Strategies to overcome these barriers included reduced emphasis on the potential superiority of the intervention to be tested, reassurance that contact with research staff was usually appreciated by participants, arrangements to talk with the family as a group about the study, and increased use of Spanish-language consent forms. PMID:11398568

  3. Obtaining family consent for participation in Alzheimer's research in a Cuban-American population: strategies to overcome the barriers.

    PubMed

    Williams, C L; Tappen, R; Buscemi, C; Rivera, R; Lezcano, J

    2001-01-01

    Cultural values and beliefs affect family attitudes toward participation in research. Significant resistance to allowing their elders with dementia to participate in clinical research was encountered in Cuban-American families. These families expressed concern about disturbing the elder's comfort (tranquilidad) and solitude (soledad). Furthermore, most believed that intervention would be futile. Feelings of guilt associated with nursing home placement may have been exacerbated by the suggestion that active intervention could be effective. Strategies to overcome these barriers included reduced emphasis on the potential superiority of the intervention to be tested, reassurance that contact with research staff was usually appreciated by participants, arrangements to talk with the family as a group about the study, and increased use of Spanish-language consent forms.

  4. Pregnancy options counseling for adolescents: overcoming barriers to care and preserving preference.

    PubMed

    Dobkin, Loren M; Perrucci, Alissa C; Dehlendorf, Christine

    2013-04-01

    Current clinical guidelines for counseling adolescent patients about their pregnancy options fail to give concrete suggestions for how to begin and hold conversations that support patient autonomy, provide accurate and unbiased information, and address barriers to care. Recent research suggests that relative to adult women, adolescents are at increased risk of being denied abortion because they present beyond facilities' gestational age limits. Counseling that neglects to address the structural and developmental challenges that adolescents face when seeking care may contribute to the risk of abortion denial as well as subsequent delays in prenatal care. The task of providing non-directive, patient-centered, evidence-based pregnancy options counseling to an adolescent while ensuring that she receives her chosen course of care in a timely manner is challenging. This article presents a shared decision-making framework and specific suggestions for healthcare providers to support adolescent patients in coming to their decision about whether to continue or terminate an unplanned pregnancy and access follow-up care within the current sociopolitical environment.

  5. 'Fit to fly': overcoming barriers to preoperative haemoglobin optimization in surgical patients.

    PubMed

    Muñoz, M; Gómez-Ramírez, S; Kozek-Langeneker, S; Shander, A; Richards, T; Pavía, J; Kehlet, H; Acheson, A G; Evans, C; Raobaikady, R; Javidroozi, M; Auerbach, M

    2015-07-01

    In major surgery, the implementation of multidisciplinary, multimodal and individualized strategies, collectively termed Patient Blood Management, aims to identify modifiable risks and optimise patients' own physiology with the ultimate goal of improving outcomes. Among the various strategies utilized in Patient Blood Management, timely detection and management of preoperative anaemia is most important, as it is in itself a risk factor for worse clinical outcome, but also one of the strongest predisposing factors for perioperative allogeneic blood transfusion, which in turn increases postoperative morbidity, mortality and costs. However, preoperative anaemia is still frequently ignored, with indiscriminate allogeneic blood transfusion used as a 'quick fix'. Consistent with reported evidence from other medical specialties, this imprudent practice continues to be endorsed by non-evidence based misconceptions, which constitute serious barriers for a wider implementation of preoperative haemoglobin optimisation. We have reviewed a number of these misconceptions, which we unanimously consider should be promptly abandoned by health care providers and replaced by evidence-based strategies such as detection, diagnosis and proper treatment of preoperative anaemia. We believe that this approach to preoperative anaemia management may be a viable, cost-effective strategy that is beneficial both for patients, with improved clinical outcomes, and for health systems, with more efficient use of finite health care resources.

  6. Nanoparticle-mediated brain drug delivery: Overcoming blood-brain barrier to treat neurodegenerative diseases.

    PubMed

    Saraiva, Cláudia; Praça, Catarina; Ferreira, Raquel; Santos, Tiago; Ferreira, Lino; Bernardino, Liliana

    2016-08-10

    The blood-brain barrier (BBB) is a vital boundary between neural tissue and circulating blood. The BBB's unique and protective features control brain homeostasis as well as ion and molecule movement. Failure in maintaining any of these components results in the breakdown of this specialized multicellular structure and consequently promotes neuroinflammation and neurodegeneration. In several high incidence pathologies such as stroke, Alzheimer's (AD) and Parkinson's disease (PD) the BBB is impaired. However, even a damaged and more permeable BBB can pose serious challenges to drug delivery into the brain. The use of nanoparticle (NP) formulations able to encapsulate molecules with therapeutic value, while targeting specific transport processes in the brain vasculature, may enhance drug transport through the BBB in neurodegenerative/ischemic disorders and target relevant regions in the brain for regenerative processes. In this review, we will discuss BBB composition and characteristics and how these features are altered in pathology, namely in stroke, AD and PD. Additionally, factors influencing an efficient intravenous delivery of polymeric and inorganic NPs into the brain as well as NP-related delivery systems with the most promising functional outcomes will also be discussed.

  7. OVERCOMING BARRIERS To DIVERSITY IN CHIROPRACTIC PATIENT AND PRACTITIONER POPULATIONS: A COMMENTARY.

    PubMed

    Young, Kenneth J

    2015-01-01

    Increasing the diversity of practitioner and patient populations has been identified as a worthy goal in the chiropractic profession, which has predominantly white male practitioners and white female patients in the USA. Toward that end, 'diversity' has been the topic of several papers and was the theme of a 2012 conference of chiropractic educators. However, generally just the microcosm of the interactions of practitioners with patients or teachers with students has been discussed. The macrocosm of larger societal issues and government policies has not been broached. Examples of issues and policies that affect diversity within a profession include portrayals of, and value judgements on diversity by the media and politicians, as well as public funding for healthcare and education. Diversity was defined in this paper to mean differences in race, sex, sexual orientation, economic status, ethnicity, religion and other life circumstances in a population. The purpose of this paper is to raise awareness of evidence that social issues and government policy affect the diversity of practitioners and patients, and to suggest that the barriers to diversity present in these realms be addressed with a cogent, profession-wide effort in order to help increase the diversity of people involved with chiropractic. PMID:26647486

  8. OVERCOMING BARRIERS To DIVERSITY IN CHIROPRACTIC PATIENT AND PRACTITIONER POPULATIONS: A COMMENTARY.

    PubMed

    Young, Kenneth J

    2015-01-01

    Increasing the diversity of practitioner and patient populations has been identified as a worthy goal in the chiropractic profession, which has predominantly white male practitioners and white female patients in the USA. Toward that end, 'diversity' has been the topic of several papers and was the theme of a 2012 conference of chiropractic educators. However, generally just the microcosm of the interactions of practitioners with patients or teachers with students has been discussed. The macrocosm of larger societal issues and government policies has not been broached. Examples of issues and policies that affect diversity within a profession include portrayals of, and value judgements on diversity by the media and politicians, as well as public funding for healthcare and education. Diversity was defined in this paper to mean differences in race, sex, sexual orientation, economic status, ethnicity, religion and other life circumstances in a population. The purpose of this paper is to raise awareness of evidence that social issues and government policy affect the diversity of practitioners and patients, and to suggest that the barriers to diversity present in these realms be addressed with a cogent, profession-wide effort in order to help increase the diversity of people involved with chiropractic.

  9. 'Fit to fly': overcoming barriers to preoperative haemoglobin optimization in surgical patients.

    PubMed

    Muñoz, M; Gómez-Ramírez, S; Kozek-Langeneker, S; Shander, A; Richards, T; Pavía, J; Kehlet, H; Acheson, A G; Evans, C; Raobaikady, R; Javidroozi, M; Auerbach, M

    2015-07-01

    In major surgery, the implementation of multidisciplinary, multimodal and individualized strategies, collectively termed Patient Blood Management, aims to identify modifiable risks and optimise patients' own physiology with the ultimate goal of improving outcomes. Among the various strategies utilized in Patient Blood Management, timely detection and management of preoperative anaemia is most important, as it is in itself a risk factor for worse clinical outcome, but also one of the strongest predisposing factors for perioperative allogeneic blood transfusion, which in turn increases postoperative morbidity, mortality and costs. However, preoperative anaemia is still frequently ignored, with indiscriminate allogeneic blood transfusion used as a 'quick fix'. Consistent with reported evidence from other medical specialties, this imprudent practice continues to be endorsed by non-evidence based misconceptions, which constitute serious barriers for a wider implementation of preoperative haemoglobin optimisation. We have reviewed a number of these misconceptions, which we unanimously consider should be promptly abandoned by health care providers and replaced by evidence-based strategies such as detection, diagnosis and proper treatment of preoperative anaemia. We believe that this approach to preoperative anaemia management may be a viable, cost-effective strategy that is beneficial both for patients, with improved clinical outcomes, and for health systems, with more efficient use of finite health care resources. PMID:26089443

  10. Identifying and Overcoming Critical Barriers to Widespread Second Use of PEV Batteries

    SciTech Connect

    Neubauer, J.; Smith, K.; Wood, E.; Pesaran, A.

    2015-02-01

    Both the market penetration of plug-in electric vehicles (PEVs) and deployment of grid-connected energy storage systems are presently restricted by the high cost of batteries. Battery second use (B2U) strategies--in which a single battery first serves an automotive application, then is redeployed into a secondary market--could help address both issues by reducing battery costs to the primary (automotive) and secondary (electricity grid) users. This study investigates the feasibility of and major barriers to the second use of lithium-ion PEV batteries by posing and answering the following critical B2U questions: 1. When will used automotive batteries become available, and how healthy will they be? 2. What is required to repurpose used automotive batteries, and how much will it cost? 3. How will repurposed automotive batteries be used, how long will they last, and what is their value? Advanced analysis techniques are employed that consider the electrical, thermal, and degradation response of batteries in both the primary (automotive) and secondary service periods. Second use applications are treated in detail, addressing operational requirements, economic value, and market potential. The study concludes that B2U is viable and could provide considerable societal benefits due to the large possible supply of repurposed automotive batteries and substantial remaining battery life following automotive service. However, the only identified secondary market large enough to consume the supply of these batteries (utility peaker plant replacement) is expected to be a low margin market, and thus B2U is not expected to affect the upfront cost of PEVs.

  11. Applying Risk Science and Stakeholder Engagement to Overcome Environmental Barriers to Marine and Hydrokinetic Energy Projects

    SciTech Connect

    Copping, Andrea E.; Anderson, Richard M.; Van Cleve, Frances B.

    2010-09-20

    The production of electricity from the moving waters of the ocean has the potential to be a viable addition to the portfolio of renewable energy sources worldwide. The marine and hydrokinetic (MHK) industry faces many hurdles, including technology development, challenges of offshore deployments, and financing; however, the barrier most commonly identified by industry, regulators, and stakeholders is the uncertainty surrounding potential environmental effects of devices placed in the water and the permitting processes associated with real or potential impacts. Regulatory processes are not well positioned to judge the severity of harm due to turbines or wave generators. Risks from MHK devices to endangered or protected animals in coastal waters and rivers, as well as the habitats that support them, are poorly understood. This uncertainty raises concerns about catastrophic interactions between spinning turbine blades or slack mooring lines and marine mammals, birds and fish. In order to accelerate the deployment of tidal and wave devices, there is a need to sort through the extensive list of potential interactions that may cause harm to marine organisms and ecosystems, to set priorities for regulatory triggers, and to direct future research. Identifying the risk of MHK technology components on specific marine organisms and ecosystem components can separate perceived from real risk-relevant interactions. Scientists from Pacific Northwest National Laboratory (PNNL) are developing an Environmental Risk Evaluation System (ERES) to assess environmental effects associated with MHK technologies and projects through a systematic analytical process, with specific input from key stakeholder groups. The array of stakeholders interested in the development of MHK is broad, segmenting into those whose involvement is essential for the success of the MHK project, those that are influential, and those that are interested. PNNL and their partners have engaged these groups, gaining

  12. Supramolecular association via Sb...S and C-H...S interactions in dimeric tris(N,N-dimethyldithiocarbamato-S,S')antimony(III): an approach to overcome the concept of steric bulk on such interactions.

    PubMed

    Chauhan, H P S; Carpenter, Jaswant

    2013-12-01

    Tris(N,N-dimethyldithiocarbamato-S,S')antimony(III) has been isolated as a dimer in acetonitrile. Single-crystal X-ray analysis shows that the molecule possesses both Sb···S and C-H···S interactions, which results in a supramolecular association in the absence of hydrogen-bonding functionality on the R group. The co-existence in the title compound of such interactions is a unique character of known dimeric antimony(III) alkyl and/or aryl dithiocarbamate complexes. The literature reveals that the species where the alkyl and/or aryl dithiocarbamates carry the following groups: R = methyl (chloroform solvated), ethyl, n-propyl, pyrrolidine, morpholine, piperidine, azepane, benzyl, methylphenyl, are not capable of forming significant hydrogen-bonding interactions. However, either Sb···S or C-H···S intermolecular interactions dominate between two centrosymmetrically related molecules leading to a supramolecular aggregation. In the species where the R group carries hydrogen-bonding functionality, i.e. 2-hydroxylethyl, the C-H···S interactions are subverted by O-H···O hydrogen bonding. In addition, the title compound does not have steric hindrance or any hydrogen-bonding group but is stabilized with the co-existence of Sb···S and C-H···S interactions. Analysis of the secondary interactions of a series of analogues previously reported reveals that steric bulk is unnecessary for the mitigation of Sb···S interactions and for the establishment of C-H···S secondary bonding. PMID:24253087

  13. Performance of some new Niño3.4 predictors at overcoming the spring predictability barrier.

    NASA Astrophysics Data System (ADS)

    Miguel, Tasambay-Salazar; Jose, Ortizbevia Maria; Francisco Jose, Alvarez-Garcia; Antonio, Ruizdeelvira

    2016-04-01

    The El Niño-Southern Oscillation (ENSO) phenomenon is the main source of predictability skill in many regions of the world, at seasonal and interannual timescales. Improving ENSO understanding and forecast skill is still one of the main goals of the international seasonal forecast programs. A common feature found in ENSO forecast is the skill predictability barrier, that is the skill drop for forecast across the spring season. In this study ENSO variability is represented by the Niño3.4 Index. Here we will use different seasonal linear stochastic models to test the performance of some new ENSO predictors at overcoming the spring predictability barrier. The benchmarkt is the performance scored by the same predictive scheme when the variables are those of a basic equatorial model representing the 'recharge-discharge' oscillator paradigm. Some of the new predictors, like the Tropical South Atlantic Index, the Tropical North Atlantic Index, the Indian Ocean Dipole Mode or the Pacific Meridional Model have been pointed at by recent studies. Additionally, we propose two new predictors, that take into account the zonal sea surface temperature gradients across the tropical Pacific, the North Tropical Pacific Zonal Gradient and the South Tropical Pacific Zonal Gradient Indexes. We intercompare the performance of the new predictors, by introducing them, one at a time, in a simple, three variables, stochastic predictive scheme. For some seasons and lags, the differences between the skill scored by some of the models that include one of these predictors are important. However, these are diminished when a Full Stochastic Mode set-up is adopted. References. Tasambay Salazar, M.; Ortiz Beviá, M. J.; Alvarez García, F. J.; Ruiz de Elvira Serra, A. The Niño3.4 region predictability beyond the persistence barrier. Tellus A. 2015, 67. doi: 10.3402/tellusa.v67.27457,

  14. The use of inhibitory agents to overcome the enzymatic barrier to perorally administered therapeutic peptides and proteins.

    PubMed

    Bernkop-Schnürch, A

    1998-03-01

    The peroral administration of peptide drugs is a major challenge to pharmaceutical science. In order to provide a sufficient bioavailability of these therapeutic agents after oral dosing, several barriers encountered with the gastrointestinal (GI) tract have to be overcome by a suitable galenic. One of these barriers is caused by proteolytic enzymes, leading to a severe presystemic degradation in the GI tract. Besides some other strategies to overcome the so-called enzymatic barrier, the use of inhibitory agents has gained considerable scientific interest, as various in vivo studies could demonstrate a significantly improved bioavailability of therapeutic peptides and proteins, due to the co-administration of such excipients. In vitro techniques to evaluate the actual potential of inhibitory agents incubation with pure proteases, freshly collected gastric or intestinal fluids, mucosal homogenates, brush border vesicles and freshly excised mucosa. In situ techniques are based on single-pass perfusion studies cannulating different intestinal segments and determining the amount of undegraded model drug in perfusion solutions or blood. For in vivo studies, insulin is mostly used as a model drug, offering the advantage of a well-established method to evaluate the biological response after oral dosing by determining the decrease in blood glucose level. Generally, inhibitory agents can be divided into: inhibitors which are not based on amino acids (I), such as p-aminobenzamidine, FK-448 and camostat mesilate; amino acids and modified amino acids (II), such acid derivatives; peptides and modified peptides (III), e.g. bacitracin, antipain, chymostatin and amastatin; and polypeptide protease inhibitors (IV), e.g. aprotinin, Bowman-Birk inhibitor and soybean trypsin inhibitor. Furthermore, complexing agents and some mucoadhesive polymers also display enzyme inhibitory activity. Drawbacks of inhibitory agents, such the risk of toxic side effects or high production costs, might

  15. Barriers to integration of behavioral and social sciences in the general medicine curriculum and recommended strategies to overcome them: A systematic review

    PubMed Central

    TABATABAEI, ZAHRA; YAZDANI, SHAHRAM; SADEGHI, RAMIN

    2016-01-01

    Introduction The integration of behavioral and social sciences (BSS) into the curriculum of medical students in order to equip them with the necessary knowledge, skills and attitudes is an essential issue, emphasized in many researches. Our aim is to investigate the barriers to integrate BSS into the general medicine curriculum as well as the recommended strategies to overcome such barriers through a systematic review of literature. Methods PubMed, ERIC, Scopus, CINAHL, Google Scholar, and OPENGREY were searched for studies on the barriers to integration of BSS into the general medicine curriculum as well as the strategies employed to overcome them until August 28, 2015. Results Sixteen relevant studies were included and the related domains were categorized as barriers and some strategies were recommended to overcome them. In addition, the quality of the included studies was assessed. Conclusion Despite the prominent role of BSS in the effectiveness of health care, these sciences have not been included in the curriculum of medical students effectively. The identified barriers and the strategies used to overcome them should be considered for all integration programs. Future studies should focus on the process of BSS integration in the medical curricula and should evaluate the efficacy of this integration in more detail. PMID:27382578

  16. The GEOFAR Project - Geothermal Finance and Awareness in Europeans Regions - Development of new schemes to overcome non-technical barriers, focusing particularly on financial barriers

    NASA Astrophysics Data System (ADS)

    Poux, Adeline; Wendel, Marco; Jaudin, Florence; Hiegl, Mathias

    2010-05-01

    Numerous advantages of geothermal energy like its widespread distribution, a base-load power and availability higher than 90%, a small footprint and low carbon emissions, and the growing concerns about climate changes strongly promote the development of geothermal projects. Geothermal energy as a local energy source implies needs on surface to be located close to the geothermal resource. Many European regions dispose of a good geothermal potential but it is mostly not sufficiently developed due to non-technical barriers occurring at the very early stages of the project. The GEOFAR Project carried out within the framework of EU's "Intelligent Energy Europe" (IEE) program, gathers a consortium of European partners from Germany, France, Greece, Spain and Portugal. Launched in September 2008, the aim of this research project is to analyze the mentioned non-technical barriers, focusing most particularly on economic and financial aspects. Based on this analysis GEOFAR aims at developing new financial and administrative schemes to overcome the main financial barriers for deep geothermal projects (for electricity and direct use, without heat pumps). The analysis of the current situation and the future development of geothermal energy in GEOFAR target countries (Germany, France, Greece, Spain, Portugal, Slovakia, Bulgaria and Hungary) was necessary to understand and expose the diverging status of the geothermal sector and the more and less complicated situation for geothermal projects in different Europeans Regions. A deeper analysis of 40 cases studies (operating, planned and failed projects) of deep geothermal projects also contributed to this detailed view. An exhaustive analysis and description of financial mechanisms already existing in different European countries and at European level to support investors completed the research on non-technical barriers. Based on this profound analysis, the GEOFAR project has made an overview of the difficulties met by project

  17. Overcoming the Illiteracy Barrier.

    ERIC Educational Resources Information Center

    Park, Rosemarie J.

    1984-01-01

    This article asks "How literate do workers need to be?" and suggests such measures as the widespread use of technical materials written in "plain language" and employers' offering job-related reading programs. (JB)

  18. The role of "blebbing" in overcoming the hydrophobic barrier during biooxidation of elemental sulfur by Thiobacillus thiooxidans

    USGS Publications Warehouse

    Knickerbocker, C.; Nordstrom, D.K.; Southam, G.

    2000-01-01

    Brimstone Basin, in southeastern Yellowstone National Park, Wyoming is an ancient hydrothermal area containing solfataric alteration. Drainage waters flowing from Brimstone Basin had pH values as low as 1.23 and contained up to 1.7×106 MPN/ml acidophilic sulfur-oxidizing bacteria. Thiobacillus thiooxidans was the dominant sulfur-oxidizing bacterium recovered from an enrichment culture and was used in a structural examination of bacterial sulfur oxidation. Growth in these sulfur cultures occurred in two phases with cells in association with the macroscopic sulfur grains and in suspension above these grains. Colonization of sulfur grains by individual cells and microcolonies was facilitated by organic material that appeared to be responsible for bacterial adhesion. Transmission electron microscopy of negatively stained (2% [wt./vol.] uranyl acetate), sulfur-grown T. thiooxidans revealed extensive membrane blebbing (sloughing of outer membrane vesicles) and the presence of approximately 100 nm sized sulfur particles adsorbed to membrane material surrounding individual bacteria. Sulfite-grown bacteria did not possess membrane blebs. The amphipathic nature of these outer membrane vesicles appear to be responsible for overcoming the hydrophobic barrier necessary for the growth of T. thiooxidans on elemental sulfur.

  19. Overcoming access barriers to health services through membership-based microfinance organizations: a review of evidence from South Asia

    PubMed Central

    Saha, Somen; Annear, Peter Leslie

    2015-01-01

    It is a challenge for the poor to overcome the barriers to accessing health services. Membership-based microfinance with associated health programmes can improve health outcomes for the poor. This study reviewed the evidence published between 1993 and 2013 on the role of membership-based microfinance with associated health programmes in improving health outcomes for the poor in South Asia. A total of 661 papers were identified and 26 selected for inclusion, based on the relevance and rigour of the research methods. Of these 26, five were evidence reviews. Of the remaining 21 papers, 12 were from India, seven from Bangladesh, and one each from Sri Lanka and Indonesia. Three papers addressed more than one theme. Five key themes emerged from the review: (i) the impact of microfinance programmes on the social and economic situation of the poor; (ii) the impact of microfinance programmes on community health; (iii) the impact of integrated microfinance health programmes on raising client awareness; (iv) the impact of integrated microfinance health programmes on financing health care; and (v) the impact of integrated microfinance health programmes on affordable health-care products and services. The review provides new evidence on the pathways through which microfinance helps to improve population health and value for money for such programmes. Among countries with large populations in the informal sector, there is a strong case for policy-makers to support these groups in providing access to life-saving health care among the poor. PMID:25685728

  20. Effective Strategies to Overcome the Barriers of Poverty in Large Comprehensive High Schools with a Large Minority and Severely Economically Disadvantaged Population

    ERIC Educational Resources Information Center

    Sheffield, Lynne M.

    2012-01-01

    Purpose: The purpose of this study was to identify effective strategies used by principals of high-poverty, large high schools with more than 70% minority student population, that overcome the barriers identified for high poverty in the literature. Methodology: Descriptive research was used to gather qualitative and quantitative data to identify…

  1. Overcoming the diffusion barrier of mucus and absorption barrier of epithelium by self-assembled nanoparticles for oral delivery of insulin.

    PubMed

    Shan, Wei; Zhu, Xi; Liu, Min; Li, Lian; Zhong, Jiaju; Sun, Wei; Zhang, Zhirong; Huang, Yuan

    2015-03-24

    Nanoparticles (NPs) have demonstrated great potential for the oral delivery of protein drugs that have very limited oral bioavailability. Orally administered NPs could be absorbed by the epithelial tissue only if they successfully permeate through the mucus that covers the epithelium. However, efficient epithelial absorption and mucus permeation require very different surface properties of a nanocarrier. We herein report self-assembled NPs for efficient oral delivery of insulin by facilitating both of these two processes. The NPs possess a nanocomplex core composed of insulin and cell penetrating peptide (CPP), and a dissociable hydrophilic coating of N-(2-hydroxypropyl) methacrylamide copolymer (pHPMA) derivatives. After systematic screening using mucus-secreting epithelial cells, NPs exhibit excellent permeation in mucus due to the "mucus-inert" pHPMA coating, as well as high epithelial absorption mediated by CPP. The investigation of NP behavior shows that the pHPMA molecules gradually dissociate from the NP surface as it permeates through mucus, and the CPP-rich core is revealed in time for subsequent transepithelial transport through the secretory endoplasmic reticulum/Golgi pathway and endocytic recycling pathway. The NPs exhibit 20-fold higher absorption than free insulin on mucus-secreting epithelium cells, and orally administered NPs generate a prominent hypoglycemic response and an increase of the serum insulin concentration in diabetic rats. Our study provides the evidence of using pHPMA as dissociable "mucus-inert" agent to enhance mucus permeation of NPs, and validates a strategy to overcome the multiple absorption barriers using NP platform with dissociable hydrophilic coating and drug-loaded CPP-rich core.

  2. Sequence-Specific, RNA–Protein Interactions Overcome Electrostatic Barriers Preventing Assembly of Satellite Tobacco Necrosis Virus Coat Protein

    PubMed Central

    Ford, Robert J.; Barker, Amy M.; Bakker, Saskia E.; Coutts, Robert H.; Ranson, Neil A.; Phillips, Simon E.V.; Pearson, Arwen R.; Stockley, Peter G.

    2013-01-01

    We have examined the roles of RNA–coat protein (CP) interactions in the assembly of satellite tobacco necrosis virus (STNV). The viral genomic RNA encodes only the CP, which comprises a β-barrel domain connected to a positively charged N-terminal extension. In the previous crystal structures of this system, the first 11 residues of the protein are disordered. Using variants of an RNA aptamer sequence isolated against the CP, B3, we have studied the sequence specificity of RNA-induced assembly. B3 consists of a stem–loop presenting the tetra-loop sequence ACAA. There is a clear preference for RNAs encompassing this loop sequence, as measured by the yield of T = 1 capsids, which is indifferent to sequences within the stem. The B3-containing virus-like particle has been crystallised and its structure was determined to 2.3 Å. A lower-resolution map encompassing density for the RNA has also been calculated. The presence of B3 results in increased ordering of the N-terminal helices located at the particle 3-fold axes, which extend by roughly one and a half turns to encompass residues 8–11, including R8 and K9. Under assembly conditions, STNV CP in the absence of RNA is monomeric and does not self-assemble. These facts suggest that a plausible model for assembly initiation is the specific RNA-induced stabilisation of a trimeric capsomere. The basic nature of the helical extension suggests that electrostatic repulsion between CPs prevents assembly in the absence of RNA and that this barrier is overcome by correct placement of appropriately orientated helical RNA stems. Such a mechanism would be consistent with the data shown here for assembly with longer RNA fragments, including an STNV genome. The results are discussed in light of a first stage of assembly involving compaction of the genomic RNA driven by multiple RNA packaging signal–CP interactions. PMID:23318955

  3. "My hair or my health:" Overcoming barriers to physical activity in African American women with a focus on hairstyle-related factors.

    PubMed

    Huebschmann, Amy G; Campbell, Lucille Johnson; Brown, Candace S; Dunn, Andrea L

    2016-01-01

    Physical activity disparities among African American (AA) women may be related to sociocultural barriers, including difficulties with restyling hair after exercise. We sought to identify physical activity barriers and facilitators in AA women with a focus on sociocultural factors related to hairstyle maintenance. Participants (n = 51) were AA women aged 19-73 years who completed valid surveys and participated in structured focus groups, stratified by age and physical activity levels, from November 2012 to February 2013. The Constant Comparison method was used to develop qualitative themes for barriers and facilitators. The most frequently reported general physical activity barrier among exercisers was "lack of money" (27%) and among non-exercisers was "lack of self-discipline" (57%). A hairstyle-related barrier of "sweating out my hairstyle" was reported by 7% of exercisers and 29% of non-exercisers. This hairstyle-related barrier included the need for extra time and money to restyle hair due to perspiration. Hairstyle-related facilitators included: prioritizing health over hairstyle and high self-efficacy to restyle hair after perspiration. Participants were interested in resources to simplify hairstyle maintenance. AA women whose hairstyle is affected by perspiration may avoid physical activity due to time and financial burdens. Increasing self-efficacy to restyle hair after perspiration may help to overcome this barrier.

  4. What are the barriers which discourage 15-16 year-old girls from participating in team sports and how can we overcome them?

    PubMed

    Wetton, Abigail R; Radley, Rebecca; Jones, Angela R; Pearce, Mark S

    2013-01-01

    Given the clear benefits of regular physical activity (such as reduced risks of cardiovascular disease and obesity, as well as other benefits including those related to mental health), exploration of the reasons that adolescent girls give for not taking part in team sports may be particularly valuable for enhancing later rates of participation. We combined questionnaires (n = 60) and semistructured interviews (n = 6) to assess the barriers that prevent 15-16-year-old girls from participating in extracurricular team games and what can be done to overcome these barriers and improve physical activity levels. Four barriers became prominent as to why girls in this sample do not participate: Internal Factors, Existing Stereotypes, Other Hobbies and Teachers. Methods to overcome these barriers were identified; changing teachers' attitudes and shifting the media's focus away from male sport. Following the successful summer Olympics and Paralympics in the UK, and the resulting positive focus on some of the nation's female athletes, a shift in focus may be possible. However, this needs to be maintained to allow girls more opportunities, role models and motivation to participate in sport. PMID:24073416

  5. What are the barriers which discourage 15-16 year-old girls from participating in team sports and how can we overcome them?

    PubMed

    Wetton, Abigail R; Radley, Rebecca; Jones, Angela R; Pearce, Mark S

    2013-01-01

    Given the clear benefits of regular physical activity (such as reduced risks of cardiovascular disease and obesity, as well as other benefits including those related to mental health), exploration of the reasons that adolescent girls give for not taking part in team sports may be particularly valuable for enhancing later rates of participation. We combined questionnaires (n = 60) and semistructured interviews (n = 6) to assess the barriers that prevent 15-16-year-old girls from participating in extracurricular team games and what can be done to overcome these barriers and improve physical activity levels. Four barriers became prominent as to why girls in this sample do not participate: Internal Factors, Existing Stereotypes, Other Hobbies and Teachers. Methods to overcome these barriers were identified; changing teachers' attitudes and shifting the media's focus away from male sport. Following the successful summer Olympics and Paralympics in the UK, and the resulting positive focus on some of the nation's female athletes, a shift in focus may be possible. However, this needs to be maintained to allow girls more opportunities, role models and motivation to participate in sport.

  6. What Are the Barriers Which Discourage 15-16 Year-Old Girls from Participating in Team Sports and How Can We Overcome Them?

    PubMed Central

    Wetton, Abigail R.; Jones, Angela R.; Pearce, Mark S.

    2013-01-01

    Given the clear benefits of regular physical activity (such as reduced risks of cardiovascular disease and obesity, as well as other benefits including those related to mental health), exploration of the reasons that adolescent girls give for not taking part in team sports may be particularly valuable for enhancing later rates of participation. We combined questionnaires (n = 60) and semistructured interviews (n = 6) to assess the barriers that prevent 15-16-year-old girls from participating in extracurricular team games and what can be done to overcome these barriers and improve physical activity levels. Four barriers became prominent as to why girls in this sample do not participate: Internal Factors, Existing Stereotypes, Other Hobbies and Teachers. Methods to overcome these barriers were identified; changing teachers' attitudes and shifting the media's focus away from male sport. Following the successful summer Olympics and Paralympics in the UK, and the resulting positive focus on some of the nation's female athletes, a shift in focus may be possible. However, this needs to be maintained to allow girls more opportunities, role models and motivation to participate in sport. PMID:24073416

  7. Advocating for responsible oil and natural gas extraction policies; FracTracker as a mechanism for overcoming the barriers to scientific advocacy for academics and communities

    NASA Astrophysics Data System (ADS)

    Ferrar, K. J.; Malone, S.; Kelso, M.; Lenker, B.

    2013-12-01

    The inability to translate data to scientific information that can readily be incorporated by citizens into the public arena is an obstacle for science-based advocacy. This issue is particularly poignant for shale oil and natural gas development via hydraulic fracturing, as the issue has become highly politicized. Barriers to engaging in policy debate are different but highly related for community members and scientists. For citizens and interest groups, barriers including accessibility, public awareness and data presentation limit the motivation for community involvement in political interactions. To overcome such barriers, social researchers call for public engagement to move upstream and many call for a broad engagement of scientists in science-based advocacy. Furthermore surveys have shown that citizens, interest groups, and decision-makers share a broad desire for scientists to engage in environmental policy development. Regardless, scientists face a number of perceived barriers, with academics expressing the most resistance to overcoming the tension created by adherence to the scientific method and the need to engage with the broader society, described by Schneider (1990) as the 'double ethical bind'. For the scientific community the appeal of public dissemination of information beyond the scope of academic journals is limited for a number of reasons. Barriers include preservation of credibility, peer attitudes, training, and career trajectory. The result is a lack of translated information available to the public. This systematic analysis of the FracTracker platform provides an evaluation of where the features of the public engagement, GIS platform has been successful at overcoming these barriers to public dissemination, where the platform needs further development or is ill-suited to address these issues, and the development of FracTracker as an outlet for scientific researchers to engage with citizens. The analysis will also provide insight into what

  8. Strategies to Overcome Barriers to Implementation of Alcohol Screening and Brief Intervention in General Practice: a Delphi Study Among Healthcare Professionals and Addiction Prevention Experts.

    PubMed

    Abidi, L; Oenema, A; Nilsen, P; Anderson, P; van de Mheen, D

    2016-08-01

    Despite the evidence base, alcohol screening and brief intervention (ASBI) have rarely been integrated into routine clinical practice. The aim of this study is to identify strategies that could tackle barriers to ASBI implementation in general practice by involving primary healthcare professionals and addiction prevention experts. A three-round online Delphi study was carried out in the Netherlands. The first-round questionnaire consisted of open-ended questions to generate ideas about strategies to overcome barriers. In the second round, participants were asked to indicate how applicable they found each strategy. Items without consensus were systematically fed back with group median ratings and interquartile range (IQR) scores in the third-round questionnaire. In total, 39 out of 69 (57 %) invited participants enrolled in the first round, 214 participants completed the second round, and 144 of these (67 %) completed the third-round questionnaire. Results show that participants reached consensus on 59 of 81 strategies, such as the following: (1) use of E-learning technology, (2) symptom-specific screening by general practitioners (GPs) and/or universal screening by practice nurses, (3) reimbursement incentives, (4) supportive materials, (5) clear guidelines, (6) service provision of addiction care centers, and (7) more publicity in the media. This exploratory study identified a broad set of strategies that could potentially be used for overcoming barriers to ASBI implementation in general practice and paves the way for future research to experimentally test the identified implementation strategies using multifaceted approaches. PMID:27167074

  9. "We Don't Want to Talk about That": Overcoming Barriers to Rural Aging Research and Interventions on Sensitive Topics

    ERIC Educational Resources Information Center

    Zanjani, Faika; Rowles, Graham D.

    2012-01-01

    Geographical, economic, social and cultural barriers to accessing services in rural areas are widely reported. Less widely discussed are dilemmas posed by individual and community reluctance to address sensitive health issues. This article, focusing on the highly sensitive area of mental health, and employing a participatory action approach,…

  10. Overcoming barriers to effectiveness in a health care operational environment: building on the lessons of American industry.

    PubMed

    Zimmerer, L W; Zimmerer, T W; Yasin, M M

    1999-01-01

    Several of the manufacturing-based philosophies, techniques and tools, such as Total Quality Management (TQM), Continuous Improvement (CI), Business Process Reengineering (BPR) and Time-based Competition (TBC) have been successfully adapted for use within the service sector. Diverse service industries including airlines, insurance, food services and hospitality have increased customer satisfaction and performance through the use of the quality driven, manufacturing-based philosophies. This article explores the reasons for the limited success of TQM/CI, BPR, TBC and benchmarking within the health care industry. Sixteen barriers to change are identified, possible counter-measures to these barriers are outlined and two conceptual frameworks are offered as possible facilitators of change for the health care industry. PMID:11066723

  11. Overcoming barriers to effectiveness in a health care operational environment: building on the lessons of American industry.

    PubMed

    Zimmerer, L W; Zimmerer, T W; Yasin, M M

    1999-01-01

    Several of the manufacturing-based philosophies, techniques and tools, such as Total Quality Management (TQM), Continuous Improvement (CI), Business Process Reengineering (BPR) and Time-based Competition (TBC) have been successfully adapted for use within the service sector. Diverse service industries including airlines, insurance, food services and hospitality have increased customer satisfaction and performance through the use of the quality driven, manufacturing-based philosophies. This article explores the reasons for the limited success of TQM/CI, BPR, TBC and benchmarking within the health care industry. Sixteen barriers to change are identified, possible counter-measures to these barriers are outlined and two conceptual frameworks are offered as possible facilitators of change for the health care industry.

  12. Being "chill" with teachers and "frozen" by peers in science: overcoming social and educational barriers in a learning community

    NASA Astrophysics Data System (ADS)

    Kim, Hannah; Scantlebury, Kathryn

    2013-09-01

    This forum discusses the issue of `othering' and how intersectionality is a useful analytical framework for understanding the students' immigrant experiences in, and out of, the science classroom. We use a feminist perspective to discuss Minjung's study because gender is a key aspect of one's identity other aspects such as race, religion, socio-economic status, and age have assumed a significant status in gender studies. Lastly we examine the supports and barriers that cliques can produce and propose the importance of building a learning community in the science classroom to engage all students.

  13. Barriers to blood pressure control in African Americans. Overcoming obstacles is challenging, but target goals can be attained.

    PubMed

    Douglas, Janice G; Ferdinand, Keith C; Bakris, George L; Sowers, James R

    2002-10-01

    Outdated and biased attitudes and care standards impede optimal care of hypertension in African Americans. The negative expectations that blood pressure targets cannot be reached must be overcome by systematic and appropriate education and treatment. However, physicians should expect that (1) African American patients with elevated blood pressure benefit from early and intensive management, (2) blood pressure can be maintained at goal with appropriate therapeutic lifestyle changes and medications, and (3) complications related to high blood pressure can be avoided. To bring blood pressure down to the target goal, combination pharmacologic therapy is often required. When extensive efforts to achieve blood pressure control prove unattainable in the primary care setting, consultation with a hypertension specialist should be considered.

  14. Using community-based participatory research to identify potential interventions to overcome barriers to adolescents’ healthy eating and physical activity

    PubMed Central

    Goh, Ying-Ying; Sipple-Asher, Bessie Ko; Uyeda, Kimberly; Hawes-Dawson, Jennifer; Olarita-Dhungana, Josephina; Ryan, Gery W.; Schuster, Mark A.

    2010-01-01

    Using a community-based participatory research approach, we explored adolescent, parent, and community stakeholder perspectives on barriers to healthy eating and physical activity, and intervention ideas to address adolescent obesity. We conducted 14 adolescent focus groups (n = 119), 8 parent focus groups (n = 63), and 28 interviews with community members (i.e., local experts knowledgeable about youth nutrition and physical activity). Participants described ecological and psychosocial barriers in neighborhoods (e.g., lack of accessible nutritious food), in schools (e.g., poor quality of physical education), at home (e.g., sedentary lifestyle), and at the individual level (e.g., lack of nutrition knowledge). Participants proposed interventions such as nutrition classes for families, addition of healthy school food options that appeal to students, and non-competitive physical education activities. Participants supported health education delivered by students. Findings demonstrate that community-based participatory research is useful for revealing potentially feasible interventions that are acceptable to community members. PMID:19544091

  15. Exploring the role of social interactions and supports in overcoming accessibility barriers while undertaking health tours in India.

    PubMed

    Jana, Arnab; Harata, Noboru; Kiyoshi, Takami; Ohmori, Nobuaki

    2014-01-01

    This article explores the phenomenon of companionship as an adaptation strategy to counter the existing barriers to health care access in developing nations. Companionship is argued to be an outcome of "inter" and "intra" household collaboration to offer diverse supports in addition to altruism. The analysis of the household survey conducted in West Bengal, India, exhibited different patterns of health care tours and the associated dependencies. In addition to support in terms of mobility while traveling and companionship while waiting for the opportunity, support in terms of refuge is also found to be essential, especially for the poor while they undertake regional tours. Causal models focusing on aggregated general health tours and specific regional tours were estimated separately to comprehend the implicit social interactions and their effects on the patient as well as the companions. The research demonstrated that accessibility barriers affect not only the ill, but also those associated with them and at times adversely. Segregation of regional tours illustrated the gaps, which instigated such tours and also might aid in health infrastructure planning as a whole. PMID:24871773

  16. The Value of Companion Diagnostics: Overcoming Access Barriers to Transform Personalised Health Care into an Affordable Reality in Europe.

    PubMed

    Wurcel, Victoria; Perche, Olivier; Lesteven, Daniel; Williams, Doris-Ann; Schäfer, Birgit; Hopley, Colin; Jungwirth, Rebecca; Postulka, Anne; Pasmans, Raf; Hermansson, Lisse-Lotte; Ott, Markus; Glorioso, Valeria

    2016-01-01

    Personalised health care is an evolution, moving away from a disease-focused model of care, translating scientific and technological advances into benefits for patients, and placing them at the centre of the patients' health and care. Companion diagnostics emerge as a very specific and special group of in vitro diagnostics among the different technologies shaping the personalised health care spectrum. Companion diagnostics provide highly valuable information, allowing patients, health practitioners and payers to decide with a higher level of certainty on the potential benefits of a treatment or care pathway. Decreasing uncertainty may result in a more efficient selection of treatments and care, targeted at subpopulations that are most likely to benefit. Companion diagnostics account for a minimal portion of the already small expenditure on in vitro diagnostics (far less than 1% of total health care expenditure), and yet they provide the means to limit inefficient use of health care resources while optimising patient outcomes. It is clear that equal access to personalised health care is still an issue across the EU. One of the most common perceived barriers is affordability. The investment in companion diagnostics can provide long-term value for patients and health care systems, shifting resources to areas of need. Health systems do not fully recognise yet the value that companion diagnostics bring to make personalised health care more affordable across the EU. This inhibits patient access to personalised treatments and care, preventing improved outcomes. In many countries, market access frameworks for diagnostic tests are fragmented and not aligned with specific funding and reimbursement mechanisms, discouraging the use of these tests. Emerging evidence shows that patients are missing out on the appropriate tests and treatments while a reduction in the inefficient use of health care resources is not realised. This article outlines some of these market access

  17. The Value of Companion Diagnostics: Overcoming Access Barriers to Transform Personalised Health Care into an Affordable Reality in Europe.

    PubMed

    Wurcel, Victoria; Perche, Olivier; Lesteven, Daniel; Williams, Doris-Ann; Schäfer, Birgit; Hopley, Colin; Jungwirth, Rebecca; Postulka, Anne; Pasmans, Raf; Hermansson, Lisse-Lotte; Ott, Markus; Glorioso, Valeria

    2016-01-01

    Personalised health care is an evolution, moving away from a disease-focused model of care, translating scientific and technological advances into benefits for patients, and placing them at the centre of the patients' health and care. Companion diagnostics emerge as a very specific and special group of in vitro diagnostics among the different technologies shaping the personalised health care spectrum. Companion diagnostics provide highly valuable information, allowing patients, health practitioners and payers to decide with a higher level of certainty on the potential benefits of a treatment or care pathway. Decreasing uncertainty may result in a more efficient selection of treatments and care, targeted at subpopulations that are most likely to benefit. Companion diagnostics account for a minimal portion of the already small expenditure on in vitro diagnostics (far less than 1% of total health care expenditure), and yet they provide the means to limit inefficient use of health care resources while optimising patient outcomes. It is clear that equal access to personalised health care is still an issue across the EU. One of the most common perceived barriers is affordability. The investment in companion diagnostics can provide long-term value for patients and health care systems, shifting resources to areas of need. Health systems do not fully recognise yet the value that companion diagnostics bring to make personalised health care more affordable across the EU. This inhibits patient access to personalised treatments and care, preventing improved outcomes. In many countries, market access frameworks for diagnostic tests are fragmented and not aligned with specific funding and reimbursement mechanisms, discouraging the use of these tests. Emerging evidence shows that patients are missing out on the appropriate tests and treatments while a reduction in the inefficient use of health care resources is not realised. This article outlines some of these market access

  18. A Collaborative Care Telemedicine Intervention to Overcome Treatment Barriers for Latina Women with Depression during the Perinatal Period

    PubMed Central

    Baker-Ericzén, Mary J.; Connelly, Cynthia D.; Hazen, Andrea L.; Dueñas, Cecilia; Landsverk, John A.; Horwitz, Sarah McCue

    2013-01-01

    Maternal depression is highly prevalent (10 to 20%) during the perinatal period with rates as high as 35 to 40% for Latinas. However, few Latinas are either identified or treated during the perinatal period. To address these disparities, the Perinatal Mental Health Model (PMH) was designed to ameliorate the barriers that prevent adequate diagnoses and intervention. The PMH is a culturally sensitive, short-term telemedicine, and collaborative care intervention for addressing depression among Mexican American mothers. It attends to sociocultural and socioeconomic dimensions and is delivered by trained mental health advisors within obstetric care settings. This article describes the feasibility and acceptability of utilizing the PMH. Participants (n=79) were selected from a first year ongoing randomized trial in community obstetric clinics. The intervention seems feasible and acceptable; low-income Latinas, identified as depressed during the perinatal period, reported having access to a range of appropriate community services and high satisfaction. PMID:22709321

  19. Planet Formation in Stellar Binaries. II. Overcoming the Fragmentation Barrier in α Centauri and γ Cephei-like Systems

    NASA Astrophysics Data System (ADS)

    Rafikov, Roman R.; Silsbee, Kedron

    2015-01-01

    Planet formation in small-separation (~20 AU) eccentric binaries such as γ Cephei or α Centauri is believed to be adversely affected by the presence of the stellar companion. Strong dynamical excitation of planetesimals by the eccentric companion can result in collisional destruction (rather than growth) of 1-100 km objects, giving rise to the "fragmentation barrier" for planet formation. We revise this issue using a novel description of secular dynamics of planetesimals in binaries, which accounts for the gravity of the eccentric, coplanar protoplanetary disk, as well as gas drag. By studying planetesimal collision outcomes, we show, in contrast to many previous studies, that planetesimal growth and subsequent formation of planets (including gas giants) in AU-scale orbits within ~20 AU separation binaries may be possible, provided that the protoplanetary disks are massive (gsim 10-2 M ⊙) and only weakly eccentric (disk eccentricity <~ 0.01). These requirements are compatible with both the existence of massive (several MJ ) planets in γ Cep-like systems and the results of recent simulations of gaseous disks in eccentric binaries. Terrestrial and Neptune-like planets can also form in lower-mass disks at small (sub-AU) radii. We find that the fragmentation barrier is less of a problem in eccentric disks that are apsidally aligned with the binary orbit. Alignment gives rise to special locations, where (1) relative planetesimal velocities are low and (2) the timescale of their drag-induced radial drift is long. This causes planetesimal pileup at such locations in the disk and promotes their growth locally, helping to alleviate the timescale problem for core formation.

  20. PLANET FORMATION IN STELLAR BINARIES. II. OVERCOMING THE FRAGMENTATION BARRIER IN α CENTAURI AND γ CEPHEI-LIKE SYSTEMS

    SciTech Connect

    Rafikov, Roman R.; Silsbee, Kedron

    2015-01-10

    Planet formation in small-separation (∼20 AU) eccentric binaries such as γ Cephei or α Centauri is believed to be adversely affected by the presence of the stellar companion. Strong dynamical excitation of planetesimals by the eccentric companion can result in collisional destruction (rather than growth) of 1-100 km objects, giving rise to the ''fragmentation barrier'' for planet formation. We revise this issue using a novel description of secular dynamics of planetesimals in binaries, which accounts for the gravity of the eccentric, coplanar protoplanetary disk, as well as gas drag. By studying planetesimal collision outcomes, we show, in contrast to many previous studies, that planetesimal growth and subsequent formation of planets (including gas giants) in AU-scale orbits within ∼20 AU separation binaries may be possible, provided that the protoplanetary disks are massive (≳ 10{sup –2} M {sub ☉}) and only weakly eccentric (disk eccentricity ≲ 0.01). These requirements are compatible with both the existence of massive (several M{sub J} ) planets in γ Cep-like systems and the results of recent simulations of gaseous disks in eccentric binaries. Terrestrial and Neptune-like planets can also form in lower-mass disks at small (sub-AU) radii. We find that the fragmentation barrier is less of a problem in eccentric disks that are apsidally aligned with the binary orbit. Alignment gives rise to special locations, where (1) relative planetesimal velocities are low and (2) the timescale of their drag-induced radial drift is long. This causes planetesimal pileup at such locations in the disk and promotes their growth locally, helping to alleviate the timescale problem for core formation.

  1. Overcoming barriers to seedling regeneration during forest restoration on tropical pasture land and the potential value of woody weeds.

    PubMed

    Elgar, Amelia T; Freebody, Kylie; Pohlman, Catherine L; Shoo, Luke P; Catterall, Carla P

    2014-01-01

    Combating the legacy of deforestation on tropical biodiversity requires the conversion to forest of large areas of established pasture, where barriers to native plant regeneration include competition with pasture grasses and poor propagule supply (seed availability). In addition, initial woody plants that colonise pasture are often invasive, non-native species whose ecological roles and management in the context of forest regeneration are contested. In a restoration experiment at two 0.64 ha sites we quantified the response of native woody vegetation recruitment to (1) release from competition with introduced pasture grasses, and (2) local facilitation of frugivore-assisted seed dispersal provided by scattered woody plants and artificial bird perches. Herbicide pasture grass suppression during 20 months caused a significant but modest increase in density of native woody seedlings, together with abundant co-recruitment of the prominent non-native pioneer wild tobacco (Solanum mauritianum). Recruitment of native species was further enhanced by local structure in herbicide-treated areas, being consistently greater under live trees and dead non-native shrubs (herbicide-treated) than in open areas, and intermediate under bird perches. Native seedling recruitment comprised 28 species across 0.25 ha sampled but was dominated by two rainforest pioneers (Homalanthus novoguineensis, Polyscias murrayi). These early results are consistent with the expected increase in woody vegetation recruitment in response to release from competitive and dispersive barriers to rainforest regeneration. The findings highlight the need for a pragmatic consideration of the ecological roles of woody weeds and the potential roles of "new forests" more broadly in accelerating succession of humid tropical forest across large areas of retired agricultural land.

  2. Overcoming barriers to seedling regeneration during forest restoration on tropical pasture land and the potential value of woody weeds.

    PubMed

    Elgar, Amelia T; Freebody, Kylie; Pohlman, Catherine L; Shoo, Luke P; Catterall, Carla P

    2014-01-01

    Combating the legacy of deforestation on tropical biodiversity requires the conversion to forest of large areas of established pasture, where barriers to native plant regeneration include competition with pasture grasses and poor propagule supply (seed availability). In addition, initial woody plants that colonise pasture are often invasive, non-native species whose ecological roles and management in the context of forest regeneration are contested. In a restoration experiment at two 0.64 ha sites we quantified the response of native woody vegetation recruitment to (1) release from competition with introduced pasture grasses, and (2) local facilitation of frugivore-assisted seed dispersal provided by scattered woody plants and artificial bird perches. Herbicide pasture grass suppression during 20 months caused a significant but modest increase in density of native woody seedlings, together with abundant co-recruitment of the prominent non-native pioneer wild tobacco (Solanum mauritianum). Recruitment of native species was further enhanced by local structure in herbicide-treated areas, being consistently greater under live trees and dead non-native shrubs (herbicide-treated) than in open areas, and intermediate under bird perches. Native seedling recruitment comprised 28 species across 0.25 ha sampled but was dominated by two rainforest pioneers (Homalanthus novoguineensis, Polyscias murrayi). These early results are consistent with the expected increase in woody vegetation recruitment in response to release from competitive and dispersive barriers to rainforest regeneration. The findings highlight the need for a pragmatic consideration of the ecological roles of woody weeds and the potential roles of "new forests" more broadly in accelerating succession of humid tropical forest across large areas of retired agricultural land. PMID:24904602

  3. Overcoming barriers to seedling regeneration during forest restoration on tropical pasture land and the potential value of woody weeds

    PubMed Central

    Elgar, Amelia T.; Freebody, Kylie; Pohlman, Catherine L.; Shoo, Luke P.; Catterall, Carla P.

    2014-01-01

    Combating the legacy of deforestation on tropical biodiversity requires the conversion to forest of large areas of established pasture, where barriers to native plant regeneration include competition with pasture grasses and poor propagule supply (seed availability). In addition, initial woody plants that colonise pasture are often invasive, non-native species whose ecological roles and management in the context of forest regeneration are contested. In a restoration experiment at two 0.64 ha sites we quantified the response of native woody vegetation recruitment to (1) release from competition with introduced pasture grasses, and (2) local facilitation of frugivore-assisted seed dispersal provided by scattered woody plants and artificial bird perches. Herbicide pasture grass suppression during 20 months caused a significant but modest increase in density of native woody seedlings, together with abundant co-recruitment of the prominent non-native pioneer wild tobacco (Solanum mauritianum). Recruitment of native species was further enhanced by local structure in herbicide-treated areas, being consistently greater under live trees and dead non-native shrubs (herbicide-treated) than in open areas, and intermediate under bird perches. Native seedling recruitment comprised 28 species across 0.25 ha sampled but was dominated by two rainforest pioneers (Homalanthus novoguineensis, Polyscias murrayi). These early results are consistent with the expected increase in woody vegetation recruitment in response to release from competitive and dispersive barriers to rainforest regeneration. The findings highlight the need for a pragmatic consideration of the ecological roles of woody weeds and the potential roles of “new forests” more broadly in accelerating succession of humid tropical forest across large areas of retired agricultural land. PMID:24904602

  4. The Long Way From Government Open Data to Mobile Health Apps: Overcoming Institutional Barriers in the US Federal Government

    PubMed Central

    2014-01-01

    Background Government agencies in the United States are creating mobile health (mHealth) apps as part of recent policy changes initiated by the White House’s Digital Government Strategy. Objective The objective of the study was to understand the institutional and managerial barriers for the implementation of mHealth, as well as the resulting adoption pathways of mHealth. Methods This article is based on insights derived from qualitative interview data with 35 public managers in charge of promoting the reuse of open data through Challenge.gov, the platform created to run prizes, challenges, and the vetting and implementation of the winning and vendor-created apps. Results The process of designing apps follows three different pathways: (1) entrepreneurs start to see opportunities for mobile apps, and develop either in-house or contract out to already vetted Web design vendors; (2) a top-down policy mandates agencies to adopt at least two customer-facing mobile apps; and (3) the federal government uses a policy instrument called “Prizes and Challenges”, encouraging civic hackers to design health-related mobile apps using open government data from HealthData.gov, in combination with citizen needs. All pathways of the development process incur a set of major obstacles that have to be actively managed before agencies can promote mobile apps on their websites and app stores. Conclusions Beyond the cultural paradigm shift to design interactive apps and to open health-related data to the public, the managerial challenges include accessibility, interoperability, security, privacy, and legal concerns using interactive apps tracking citizen. PMID:25537314

  5. Socio-ecological Model as a Framework for Overcoming Barriers and Challenges in Randomized Control Trials in Minority and Underserved Communities

    PubMed Central

    Salihu, Hamisu M.; Wilson, Ronee E.; King, Lindsey M.; Marty, Phillip J.; Whiteman, Valerie E.

    2015-01-01

    Background: Numerous barriers and challenges can hinder the successful enrollment and retention of study participants in clinical trials targeting minority populations. To conduct quality research, it is important to investigate these challenges, determine appropriate strategies that are evidence-based and continue seeking methods of improvement. Methods: In this paper, we report such experiences in a registered clinical trial in an underserved minority population in the Southern part of United States. This research study is a randomized double-blind controlled clinical trial that tests the efficacy of higher-strength as compared to low-strength/standard of care folic acid to prevent fetal body and brain size reduction in pregnant women who smoke. A unique approach in this socio-behavioral, genetic-epigenetic clinical trial is that we have adopted the socio-ecological model as a functional platform to effectively achieve and maintain high participant recruitment and retention rates. Results: We highlight the barriers we have encountered in our trial and describe how we have successfully applied the socio-ecological model to overcome these obstacles. Conclusions and Global Health Implications: Our positive experience will be of utility to other researchers globally. Our fi ndings have far-reaching implications as the socio-ecological model approach is adaptable to developed and developing regions and has the potential to increase recruitment and retention of hard-to-reach populations who are typically under-represented in clinical trials. PMID:27621990

  6. Steric constraints as folding coadjuvant

    NASA Astrophysics Data System (ADS)

    Tarragó, M. E.; Rocha, Luiz F.; Dasilva, R. A.; Caliri, A.

    2003-03-01

    Through the analyses of the Miyazawa-Jernigan matrix it has been shown that the hydrophobic effect generates the dominant driving force for protein folding. By using both lattice and off-lattice models, it is shown that hydrophobic-type potentials are indeed efficient in inducing the chain through nativelike configurations, but they fail to provide sufficient stability so as to keep the chain in the native state. However, through comparative Monte Carlo simulations, it is shown that hydrophobic potentials and steric constraints are two basic ingredients for the folding process. Specifically, it is shown that suitable pairwise steric constraints introduce strong changes on the configurational activity, whose main consequence is a huge increase in the overall stability condition of the native state; detailed analysis of the effects of steric constraints on the heat capacity and configurational activity are provided. The present results support the view that the folding problem of globular proteins can be approached as a process in which the mechanism to reach the native conformation and the requirements for the globule stability are uncoupled.

  7. Collective epithelial cell invasion overcomes mechanical barriers of collagenous extracellular matrix by a narrow tube-like geometry and MMP14-dependent local softening†

    PubMed Central

    Alcaraz, Jordi; Mori, Hidetoshi; Ghajar, Cyrus M.; Brownfield, Doug; Galgoczy, Roland; Bissell, Mina J.

    2013-01-01

    Collective cell invasion (CCI) through interstitial collagenous extracellular matrix (ECM) is crucial to the initial stages of branching morphogenesis, and a hallmark of tissue repair and dissemination of certain tumors. The collagenous ECM acts as a mechanical barrier against CCI. However, the physical nature of this barrier and how it is overcome by cells remains incompletely understood. To address these questions, we performed theoretical and experimental analysis of mammary epithelial branching morphogenesis in 3D type I collagen (collagen-I) gels. We found that the mechanical resistance of collagen-I is largely due to its elastic rather than its viscous properties. We also identified two strategies utilized by mammary epithelial cells that can independently minimize ECM mechanical resistance during CCI. First, cells adopt a narrow tube-like geometry during invasion, which minimizes the elastic opposition from the ECM as revealed by theoretical modeling of the most frequent invasive shapes and sizes. Second, the stiffness of the collagenous ECM is reduced at invasive fronts due to its degradation by matrix metalloproteinases (MMPs), as indicated by direct measurements of collagen-I microelasticity by atomic force microscopy. Molecular techniques further specified that the membrane-bound MMP14 mediates degradation of collagen-I at invasive fronts. Thus, our findings reveal that MMP14 is necessary to efficiently reduce the physical restraints imposed by collagen-I during branching morphogenesis, and help our overall understanding of how forces are balanced between cells and their surrounding ECM to maintain collective geometry and mechanical stability during CCI. PMID:21993836

  8. Generation of nuclear hybrids overcoming the natural barrier of incompatibility: transfer of nuclei from Lentinula edodes into protoplasts of Coriolus versicolor.

    PubMed

    Kim, C; Choi, E C; Kim, B K

    2000-02-01

    Heterokaryotic nuclear hybrids overcoming the natural barriers of incompatibility have been studied in basidiomycetes. To produce these nuclear hybrids between incompatible mushrooms, which have several potent pharmacological effects, nuclear transfer was performed between Lentinula edodes and Coriolus versicolor. Nuclei from serine auxotrophs of Lentinula edodes, LE207 (Ser-) were transferred into the protoplasts of arginine auxotrophs of Coriolus versicolor, CV17 (Arg-), using 30% polyethylene glycol 4000 in 10 mM CaCl2-glycine solution (pH 8.0). Nuclear transfer progenies were selected by nutritional complementation on minimal media supplemented with 0.6 M sucrose. The progenies were classified based on colony morphology to L. edodes-like, C. versicolor-like and non-parental type. Most of the progenies grew slower than either parent. The number of nuclei per cell was similar but the DNA content varied between progenies. The isozyme patterns of nuclear hybrids resembled either of the parent profiles or showed a mixed profile. PMID:10728662

  9. Increasing Rural Adults' Participation in Collegial Programs: Exemplary Programs. Proceedings of the Rural Action Conference "Programs and Activities to Overcome Barriers to Rural Adult Participation in Postsecondary Education" (Blacksburg, Virginia, June 1-3, 1987).

    ERIC Educational Resources Information Center

    Sullins, W. Robert, Ed.; And Others

    Approximately 85 educators from six states participated in a regional conference designed to showcase exemplary and collaborative programs to overcome many of the barriers faced by rural adults in pursuing higher education. After the keynote address, "The Role of Adult Learning in Revitalizing Rural Communities," by Cornelia Butler Flora, the…

  10. Overcoming psychosocial and developmental barriers to blood and marrow transplantation (BMT) in an adolescent/young adult (AYA) transgender patient with chronic myelogenous leukemia.

    PubMed

    Khazal, Sajad; Abdel-Azim, Hisham; Kapoor, Neena; Mahadeo, Kris M

    2014-11-01

    Adolescents/young adults (AYAs) afflicted with cancer face unique barriers to potentially standard curative therapies, such as blood and marrow transplantation (BMT). Transgender AYAs face additional barriers and there is a dearth of published literature regarding their oncology-related experience. We present the case of an AYA male-to-female (MTF) transgender patient on cross-sex hormone therapy, with a history of Chronic Myelogenous Leukemia (CML) and significant psychosocial barriers, which initially served as a barrier to BMT at two different centers; we modified our standard consent and education process and was able to successfully proceed with BMT and subsequently cure her CML. Despite unique challenges, AYA and transgender patients with significant psychosocial barriers may achieve successful outcomes with BMT. Research is needed regarding guidelines for cross-sex hormone therapy administration for patients undergoing BMT and other issues, which may be unique to the transgender experience.

  11. The synthesis of sterically hindered amides.

    PubMed

    Schäfer, Gabriel; Bode, Jeffrey W

    2014-01-01

    Amide bond formation is one of the most important reactions due to the ubiquity of the amide functional group in pharmaceuticals and biologically active compounds. However, even the best existing methods reach their limits when it comes to the synthesis of sterically hindered amides. In this article we summarize our research in the formation of sterically hindered amides. We show that the direct coupling of Grignard reagents to isocyanates provides a facile and robust solution to this long-standing challenge and hope that this methodology will find widespread application in the synthesis of pharmaceuticals and materials. PMID:24983609

  12. A Change Agent's Facilitation Process for Overcoming the Barriers of ICT Adoption for Educational Administration--The Case of a Rural-Bangladesh Vocational Institution

    ERIC Educational Resources Information Center

    Khalid, Md. Saifuddin; Nyvang, Tom

    2014-01-01

    The factors influencing the use of information and communication technologies (ICT) as a professional and management tool outside the classroom have received little research attention. The two objectives of this research were: how do stakeholders of educational administration experience the barriers of ICT adoption, and how can they facilitate the…

  13. You can teach an old dog new tricks: a qualitative analysis of how residents of senior living communities may use the web to overcome spatial and social barriers.

    PubMed

    Winstead, Vicki; Anderson, William A; Yost, Elizabeth A; Cotten, Shelia R; Warr, Amanda; Berkowsky, Ronald W

    2013-08-01

    For adults in senior living communities, information and communication technologies (ICTs) can be used to increase and expand communication for a population that is often spatially and socially separated from the general public. Using qualitative observational data from a longitudinal study of the impact of ICT usage on the quality of life among residents in assisted and independent living communities, the authors examine whether ICTs can mitigate the effects of social and spatial barriers. The authors find that ICTs have the potential to allow individuals to transcend social and spatial barriers, providing residents with the ability to maintain and enhance social networks as well as provide a greater sense of connection to the world at large. PMID:25474761

  14. Fractional transfer of a free unpaired electron to overcome energy barriers in the formation of Fe(4+) from Fe(3+) during the core contraction of macrocycles: implication for heme distortion.

    PubMed

    Liu, Qiuhua; Zhou, Xiaochun; Liu, Haomin; Zhang, Xi; Zhou, Zaichun

    2015-03-14

    The free unpaired electron in Fe(3+) ions cannot be directly removed, and needs a transfer pathway with at least four steps to overcome the high energy barriers to form Fe(4+) ions. Fine changes in the electronic structure of Fe(3+) ions on spin conversion were identified through a deeper analysis of the diffraction, spectral and electrochemical data for six non-planar iron porphyrins. Fe(3+) ions can form four d electron tautomers as the compression of the central ion is increased. This indicates that the Fe(3+) ion undergoes a multistep electron transfer where the total energy gap of electron transfer is split into several smaller gaps to form high-valent Fe(4+) ions. We find that the interchange of these four electron tautomers is clearly related to the core size of the macrocycle in the current series. The large energy barrier to produce iron(iv) complexes is overcome through a gradient effect of multiple energy levels. In addition, a possible porphyrin Fe(3+)˙ radical may be formed from its stable isoelectronic form, porphyrin Fe(3+), under strong core contraction. These results indicate the important role of heme distortion in its catalytic oxidation functions. PMID:25609455

  15. Overcoming prejudice.

    PubMed

    Da Silva, J M; Correa, J; Terto, V

    1998-02-01

    People of African descent comprise a large proportion of Brazil's population. While racism exists in the country, it is commonly denied. Most Afro-Brazilians live in poor areas, with poor health care services, sanitation, schools, and transport. Since HIV is linked to poverty, Afro-Brazilians are more affected by HIV than is the overall population. Although Afro-Brazilians contribute to Brazil's culture, they do not benefit from that contribution. Recognizing this considerable social problem, Project Araye was created in 1996 to address issues of race and HIV. Building upon religious and cultural traditions, the project is staffed by Afro-Brazilians who are knowledgeable in both health issues and Afro-Brazilian culture. Project Araye supports a wide range of diverse community leaders in linking sexual health and HIV with other health concerns which affect Afro-Brazilians such as sickle-cell anemia, diabetes, and leprosy. One important challenge has been overcoming the target population's denial of HIV and encouraging Afro-Brazilians to accept that HIV also affects them. Community leaders include religious leaders, rap musicians, artists, and other people respected by various communities. Activities include visits to samba dance schools, Umbanda and Candomble temples, and street youth groups to provide HIV-related information.

  16. Overcoming prejudice.

    PubMed

    Da Silva, J M; Correa, J; Terto, V

    1998-02-01

    People of African descent comprise a large proportion of Brazil's population. While racism exists in the country, it is commonly denied. Most Afro-Brazilians live in poor areas, with poor health care services, sanitation, schools, and transport. Since HIV is linked to poverty, Afro-Brazilians are more affected by HIV than is the overall population. Although Afro-Brazilians contribute to Brazil's culture, they do not benefit from that contribution. Recognizing this considerable social problem, Project Araye was created in 1996 to address issues of race and HIV. Building upon religious and cultural traditions, the project is staffed by Afro-Brazilians who are knowledgeable in both health issues and Afro-Brazilian culture. Project Araye supports a wide range of diverse community leaders in linking sexual health and HIV with other health concerns which affect Afro-Brazilians such as sickle-cell anemia, diabetes, and leprosy. One important challenge has been overcoming the target population's denial of HIV and encouraging Afro-Brazilians to accept that HIV also affects them. Community leaders include religious leaders, rap musicians, artists, and other people respected by various communities. Activities include visits to samba dance schools, Umbanda and Candomble temples, and street youth groups to provide HIV-related information. PMID:12293758

  17. Tri-membrane nanoparticles produced by combining liposome fusion and a novel patchwork of bicelles to overcome endosomal and nuclear membrane barriers to cargo delivery.

    PubMed

    Yamada, Asako; Mitsueda, Asako; Hasan, Mahadi; Ueda, Miho; Hama, Susumu; Warashina, Shota; Nakamura, Takashi; Harashima, Hideyoshi; Kogure, Kentaro

    2016-03-01

    Membrane fusion is a rational strategy for crossing intracellular membranes that present barriers to liposomal nanocarrier-mediated delivery of plasmid DNA into the nucleus of non-dividing cells, such as dendritic cells. Based on this strategy, we previously developed nanocarriers consisting of a nucleic acid core particle coated with four lipid membranes [Akita, et al., Biomaterials, 2009, 30, 2940-2949]. However, including the endosomal membrane and two nuclear membranes, cells possess three intracellular membranous barriers. Thus, after entering the nucleus, nanoparticles coated with four membranes would still have one lipid membrane remaining, and could impede cargo delivery. Until now, coating a core particle with an odd number of lipid membranes was challenging. To produce nanocarriers with an odd number of lipid membranes, we developed a novel coating method involving lipid nano-discs, also known as bicelles, as a material for packaging DNA in a carrier with an odd number of lipid membranes. In this procedure, bicelles fuse to form an outer coating that resembles a patchwork quilt, which allows the preparation of nanoparticles coated with only three lipid membranes. Moreover, the transfection activity of dendritic cells with these three-membrane nanoparticles was higher than that for nanoparticles coated with four lipid membranes. In summary, we developed novel nanoparticles coated with an odd number of lipid membranes using the novel "patchwork-packaging method" to deliver plasmid DNA into the nucleus via membrane fusion. PMID:26667208

  18. Tri-membrane nanoparticles produced by combining liposome fusion and a novel patchwork of bicelles to overcome endosomal and nuclear membrane barriers to cargo delivery.

    PubMed

    Yamada, Asako; Mitsueda, Asako; Hasan, Mahadi; Ueda, Miho; Hama, Susumu; Warashina, Shota; Nakamura, Takashi; Harashima, Hideyoshi; Kogure, Kentaro

    2016-03-01

    Membrane fusion is a rational strategy for crossing intracellular membranes that present barriers to liposomal nanocarrier-mediated delivery of plasmid DNA into the nucleus of non-dividing cells, such as dendritic cells. Based on this strategy, we previously developed nanocarriers consisting of a nucleic acid core particle coated with four lipid membranes [Akita, et al., Biomaterials, 2009, 30, 2940-2949]. However, including the endosomal membrane and two nuclear membranes, cells possess three intracellular membranous barriers. Thus, after entering the nucleus, nanoparticles coated with four membranes would still have one lipid membrane remaining, and could impede cargo delivery. Until now, coating a core particle with an odd number of lipid membranes was challenging. To produce nanocarriers with an odd number of lipid membranes, we developed a novel coating method involving lipid nano-discs, also known as bicelles, as a material for packaging DNA in a carrier with an odd number of lipid membranes. In this procedure, bicelles fuse to form an outer coating that resembles a patchwork quilt, which allows the preparation of nanoparticles coated with only three lipid membranes. Moreover, the transfection activity of dendritic cells with these three-membrane nanoparticles was higher than that for nanoparticles coated with four lipid membranes. In summary, we developed novel nanoparticles coated with an odd number of lipid membranes using the novel "patchwork-packaging method" to deliver plasmid DNA into the nucleus via membrane fusion.

  19. Investigation of Functionalized Poly(N,N-dimethylacrylamide)-block-polystyrene Nanoparticles As Novel Drug Delivery System to Overcome the Blood-Brain Barrier In Vitro.

    PubMed

    Gregori, Maria; Bertani, Daniela; Cazzaniga, Emanuela; Orlando, Antonina; Mauri, Michele; Bianchi, Alberto; Re, Francesca; Sesana, Silvia; Minniti, Stefania; Francolini, Maura; Cagnotto, Alfredo; Salmona, Mario; Nardo, Luca; Salerno, Domenico; Mantegazza, Francesco; Masserini, Massimo; Simonutti, Roberto

    2015-12-01

    In the search of new drug delivery carriers for the brain, self-assembled nanoparticles (NP) were prepared from poly(N,N-dimethylacrylamide)-block-polystyrene polymer. NP displayed biocompatibility on cultured endothelial cells, macrophages and differentiated SH-SY5Y neuronal-like cells. The surface-functionalization of NP with a modified fragment of human Apolipoprotein E (mApoE) enhanced the uptake of NP by cultured human brain capillary endothelial cells, as assessed by confocal microscopy, and their permeability through a Transwell Blood Brain Barrier model made with the same cells, as assessed by fluorescence. Finally, mApoE-NP embedding doxorubicin displayed an enhanced release of drug at low pH, suggesting the potential use of these NP for the treatment of brain tumors.

  20. Community-based antiretroviral therapy programs can overcome barriers to retention of patients and decongest health services in sub-Saharan Africa: a systematic review.

    PubMed

    Decroo, Tom; Rasschaert, Freya; Telfer, Barbara; Remartinez, Daniel; Laga, Marie; Ford, Nathan

    2013-09-01

    In sub-Saharan Africa models of care need to adapt to support continued scale up of antiretroviral therapy (ART) and retain millions in care. Task shifting, coupled with community participation has the potential to address the workforce gap, decongest health services, improve ART coverage, and to sustain retention of patients on ART over the long-term. The evidence supporting different models of community participation for ART care, or community-based ART, in sub-Saharan Africa, was reviewed. In Uganda and Kenya community health workers or volunteers delivered ART at home. In Mozambique people living with HIV/AIDS (PLWHA) self-formed community-based ART groups to deliver ART in the community. These examples of community ART programs made treatment more accessible and affordable. However, to achieve success some major challenges need to be overcome: first, community programs need to be driven, owned by and embedded in the communities. Second, an enabling and supportive environment is needed to ensure that task shifting to lay staff and PLWHA is effective and quality services are provided. Finally, a long term vision and commitment from national governments and international donors is required. Exploration of the cost, effectiveness, and sustainability of the different community-based ART models in different contexts will be needed. PMID:24030268

  1. Part I: Minicircle vector technology limits DNA size restrictions on ex vivo gene delivery using nanoparticle vectors: Overcoming a translational barrier in neural stem cell therapy.

    PubMed

    Fernandes, Alinda R; Chari, Divya M

    2016-09-28

    Genetically engineered neural stem cell (NSC) transplant populations offer key benefits in regenerative neurology, for release of therapeutic biomolecules in ex vivo gene therapy. NSCs are 'hard-to-transfect' but amenable to 'magnetofection'. Despite the high clinical potential of this approach, the low and transient transfection associated with the large size of therapeutic DNA constructs is a critical barrier to translation. We demonstrate for the first time that DNA minicircles (small DNA vectors encoding essential gene expression components but devoid of a bacterial backbone, thereby reducing construct size versus conventional plasmids) deployed with magnetofection achieve the highest, safe non-viral DNA transfection levels (up to 54%) reported so far for primary NSCs. Minicircle-functionalized magnetic nanoparticle (MNP)-mediated gene delivery also resulted in sustained gene expression for up to four weeks. All daughter cell types of engineered NSCs (neurons, astrocytes and oligodendrocytes) were transfected (in contrast to conventional plasmids which usually yield transfected astrocytes only), offering advantages for targeted cell engineering. In addition to enhancing MNP functionality as gene delivery vectors, minicircle technology provides key benefits from safety/scale up perspectives. Therefore, we consider the proof-of-concept of fusion of technologies used here offers high potential as a clinically translatable genetic modification strategy for cell therapy.

  2. Adaptation to Ephemeral Habitat May Overcome Natural Barriers and Severe Habitat Fragmentation in a Fire-Dependent Species, the Bachman's Sparrow (Peucaea aestivalis)

    PubMed Central

    Cerame, Blain; Cox, James A.; Brumfield, Robb T.; Tucker, James W.; Taylor, Sabrina S.

    2014-01-01

    Bachman's Sparrow (Peucaea aestivalis) is a fire-dependent species that has undergone range-wide population declines in recent decades. We examined genetic diversity in Bachman's Sparrows to determine whether natural barriers have led to distinct population units and to assess the effect of anthropogenic habitat loss and fragmentation. Genetic diversity was examined across the geographic range by genotyping 226 individuals at 18 microsatellite loci and sequencing 48 individuals at mitochondrial and nuclear genes. Multiple analyses consistently demonstrated little genetic structure and high levels of genetic variation, suggesting that populations are panmictic. Based on these genetic data, separate management units/subspecies designations or translocations to promote gene flow among fragmented populations do not appear to be necessary. Panmixia in Bachman's Sparrow may be a consequence of an historical range expansion and retraction. Alternatively, high vagility in Bachman's Sparrow may be an adaptation to the ephemeral, fire-mediated habitat that this species prefers. In recent times, high vagility also appears to have offset inbreeding and loss of genetic diversity in highly fragmented habitat. PMID:25180939

  3. Screening for Asymptomatic Extragenital Gonorrhea and Chlamydia in Men Who Have Sex with Men: Significance, Recommendations, and Options for Overcoming Barriers to Testing.

    PubMed

    Lutz, Anthony R

    2015-03-01

    Men who have sex with men (MSM) have a disproportionately greater risk than other populations of acquiring Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (GC), the two most commonly reported notifiable diseases in the United States according to the Centers for Disease Control and Prevention (CDC). The presence of either of these diseases is a significant risk factor for the acquisition and transmission of human immunodeficiency virus (HIV). Recent studies have shown that significant rates of asymptomatic GC and CT infection are found at the extragenital oropharygeal and rectal sites in MSM, with or without concurrent urogenital infection. However, extragenital sites are not being routinely screened and, thus, many asymptomatic GC and CT infections at the oropharyngeal and rectal sites may go undiagnosed. This review will begin with the current evidence-based screening recommendations for extragenital GC and CT in MSM. This will be followed by recently reported extragenital GC and CT infection rates in asymptomatic MSM, and a discussion of the risks and potential implications of undiagnosed extragenital GC and CT infections. Finally, a discussion on the frequency of, and potential barriers to, screening will be presented with a summary of potential interventions for increasing screening frequency found in the literature. The scope of this review will focus primarily on U.S. recommendations, infection rates, and screening frequencies, with the inclusion of relevant international recommendations and studies for comparative and illustrative purposes. PMID:26790015

  4. Overcoming barriers to validation of non-animal partial replacement methods/Integrated Testing Strategies: the report of an EPAA-ECVAM workshop.

    PubMed

    Kinsner-Ovaskainen, Agnieszka; Akkan, Zerrin; Casati, Silvia; Coecke, Sandra; Corvi, Raffaella; Dal Negro, Gianni; De Bruijn, Jack; De Silva, Odile; Gribaldo, Laura; Griesinger, Claudius; Jaworska, Joanna; Kreysa, Joachim; Maxwell, Gavin; McNamee, Pauline; Price, Anna; Prieto, Pilar; Schubert, Roland; Tosti, Luca; Worth, Andrew; Zuang, Valerie

    2009-09-01

    The use of Integrated Testing Strategies (ITS) in toxicological hazard identification and characterisation is becoming increasingly common as a method for enabling the integration of diverse types of toxicology data. At present, there are no existing procedures and guidelines for the construction and validation of ITS, so a joint EPAA WG5-ECVAM workshop was held with the following objectives: a) to investigate the role of ITS and the need for validation of ITS in the different industry sectors (pharmaceuticals, cosmetics, chemicals); b) to formulate a common definition of ITS applicable across different sectors; c) to explore how and when Three Rs methods are used within ITS; and d) to propose a validation rationale for ITS and for alternative methods that are foreseen to be used within ITS. The EPAA provided a platform for comparing experiences with ITS across different industry sectors. It became clear that every ITS has to be adapted to the product type, R&D stage, and regulatory context. However, common features of ITS were also identified, and this permitted the formulation of a general definition of ITS in a regulatory context. The definition served as a basis for discussing the needs, rationale and process of formal ITS validation. One of the main conclusions was that a formal validation should not be required, unless the strategy will serve as full replacement of an in vivo study used for regulatory purposes. Finally, several challenges and bottlenecks to the ITS validation were identified, and it was agreed that a roadmap on how to address these barriers would be established by the EPAA partners. PMID:19807215

  5. Steric Effects Govern the Photoactivation of Phytochromes.

    PubMed

    Falklöf, Olle; Durbeej, Bo

    2016-04-01

    Phytochromes constitute a superfamily of photoreceptor proteins existing in two forms that absorb red (Pr) and far-red (Pfr) light. Although it is well-known that the conversion of Pr into Pfr (the biologically active form) is triggered by a Z→E photoisomerization of the linear tetrapyrrole chromophore, direct evidence is scarce as to why this reaction always occurs at the methine bridge between pyrrole rings C and D. Here, we present hybrid quantum mechanics/molecular mechanics calculations based on a high-resolution Pr crystal structure of Deinococcus radiodurans bacteriophytochrome to investigate the competition between all possible photoisomerizations at the three different (AB, BC and CD) methine bridges. The results demonstrate that steric interactions with the protein are a key discriminator between the different reaction channels. In particular, it is found that such interactions render photoisomerizations at the AB and BC bridges much less probable than photoisomerization at the CD bridge.

  6. Steric Effects Govern the Photoactivation of Phytochromes.

    PubMed

    Falklöf, Olle; Durbeej, Bo

    2016-04-01

    Phytochromes constitute a superfamily of photoreceptor proteins existing in two forms that absorb red (Pr) and far-red (Pfr) light. Although it is well-known that the conversion of Pr into Pfr (the biologically active form) is triggered by a Z→E photoisomerization of the linear tetrapyrrole chromophore, direct evidence is scarce as to why this reaction always occurs at the methine bridge between pyrrole rings C and D. Here, we present hybrid quantum mechanics/molecular mechanics calculations based on a high-resolution Pr crystal structure of Deinococcus radiodurans bacteriophytochrome to investigate the competition between all possible photoisomerizations at the three different (AB, BC and CD) methine bridges. The results demonstrate that steric interactions with the protein are a key discriminator between the different reaction channels. In particular, it is found that such interactions render photoisomerizations at the AB and BC bridges much less probable than photoisomerization at the CD bridge. PMID:26756452

  7. Resistance to Self-Direction in Learning Can Be Overcome.

    ERIC Educational Resources Information Center

    Hiemstra, Roger; Brockett, Ralph G.

    1994-01-01

    Summarizes the special issue on resistance to self-direction in learning by enumerating sources of resistance (learners, facilitators, institutions) and presenting strategies for overcoming barriers. (SK)

  8. Overcoming Barriers to Classroom Technology Integration

    ERIC Educational Resources Information Center

    Kelly, Daniel P.

    2015-01-01

    Technology-savvy teachers are often the "go to" staff members in schools for their colleagues' technology issues. These teachers are seen as leaders within their schools with respect to technology and often do not understand their peers' difficulties when bringing technology into the classroom. Understanding both the reasons teachers may…

  9. Childhood lymphoedema and 'Lymphaletics': overcoming barriers.

    PubMed

    Todd, Marie

    2016-07-14

    Primary lymphoedema is a complex condition that causes tissue swelling, usually in one or more of the limbs, but lymphatic drainage of the head, trunk or deeper organs may also be affected. It can manifest in swelling at any time from birth meaning there are a number of children affected by this condition. While it is rare in childhood there are too few professionals experienced in diagnosis and treatment, which results in delays in identification and referral to appropriate services for diagnosis and treatment. The Children's Lymphoedema Special Interest Group (CLSIG) was formed in 2010 by a group of lymphoedema specialists in a bid to raise awareness, improve service provision, and enhance practitioner knowledge. One of the aims of the group was to deliver a 'fun day' (Lymphaletics) for children with lymphoedema and their families to encourage physical activity and social interaction with children who have similar problems, and to provide a source of parent-to-parent support. This article discusses the issues for children and their families, and the aims and format of the event. PMID:27409777

  10. Overcoming language barriers when teaching interprofessional groups.

    PubMed

    Welsh, Jeanette

    2012-10-01

    The author of this article undertook a small qualitative study of the best way to prepare unscheduled care staff for team-based delivery of patient care. The study was intended to highlight problems in interprofessional training courses so that guidelines for the delivery of such courses can be developed. The findings show that trainers cannot assume that all participants in training courses understand the terminology used. This article discusses this finding further.

  11. Overcoming the cutaneous barrier with microemulsions.

    PubMed

    Lopes, Luciana B

    2014-01-01

    Microemulsions are fluid and isotropic formulations that have been widely studied as delivery systems for a variety of routes, including the skin. In spite of what the name suggests, microemulsions are nanocarriers, and their use as topical delivery systems derives from their multiple advantages compared to other dermatological formulations, such as ease of preparation, thermodynamic stability and penetration-enhancing properties. Composition, charge and internal structure have been reported as determinant factors for the modulation of drug release and cutaneous and transdermal transport. This manuscript aims at reviewing how these and other characteristics affect delivery and make microemulsions appealing for topical and transdermal administration, as well as how they can be modulated during the formulation design to improve the potential and efficacy of the final system. PMID:24590260

  12. Overcoming Barriers to Progress in Exercise Genomics

    PubMed Central

    Bouchard, Claude

    2011-01-01

    This commentary focuses on the issues of statistical power, the usefulness of hypothesis-free approaches such as in genome-wide association explorations, the necessity of expanding the research beyond common DNA variants, the advantage of combining transcriptomics with genomics, and the complexities inherent to the search for links between genotype and phenotype in exercise genomics research. PMID:21697717

  13. Overcoming the barriers to effective clinical supervision.

    PubMed

    Bush, Tony

    Clinical supervision remains one of the most misunderstood practices in modern nursing. It provides a nurturing and supportive service for nurses, helping them to reflect critically on their actions in the provision of patient care. The aim of this article is to explore and examine the current role and status of clinical supervision in the NHS. PMID:15688921

  14. Overcoming Disaster Barriers To Service All Children.

    ERIC Educational Resources Information Center

    Tramonte, Michael R.

    This paper contains an outline of a workshop designed for the disaster mental health worker. The goal of the workshop is to describe how disaster services are different from other mental health services and to provide suggestions on how to make these services more effective. The types of disasters, the anatomy of a disaster, and time phases of a…

  15. Overcoming the Cutaneous Barrier with Microemulsions

    PubMed Central

    Lopes, Luciana B.

    2014-01-01

    Microemulsions are fluid and isotropic formulations that have been widely studied as delivery systems for a variety of routes, including the skin. In spite of what the name suggests, microemulsions are nanocarriers, and their use as topical delivery systems derives from their multiple advantages compared to other dermatological formulations, such as ease of preparation, thermodynamic stability and penetration-enhancing properties. Composition, charge and internal structure have been reported as determinant factors for the modulation of drug release and cutaneous and transdermal transport. This manuscript aims at reviewing how these and other characteristics affect delivery and make microemulsions appealing for topical and transdermal administration, as well as how they can be modulated during the formulation design to improve the potential and efficacy of the final system. PMID:24590260

  16. Overcoming Learning Barriers through Knowledge Management

    ERIC Educational Resources Information Center

    Dror, Itiel E.; Makany, Tamas; Kemp, Jonathan

    2011-01-01

    The ability to learn highly depends on how knowledge is managed. Specifically, different techniques for note-taking utilize different cognitive processes and strategies. In this paper, we compared dyslexic and control participants when using linear and non-linear note-taking. All our participants were professionals working in the banking and…

  17. Overcoming the Adoption Barrier to Electric Flight

    NASA Technical Reports Server (NTRS)

    Borer, Nicholas K.; Nickol, Craig L.; Jones, Frank P.; Yasky, Richard J.; Woodham, Kurt; Fell, Jared S.; Litherland, Brandon L.; Loyselle, Patricia L.; Provenza, Andrew J.; Kohlman, Lee W.; Samuel, Aamod G.

    2016-01-01

    Electrically-powered aircraft can enable dramatic increases in efficiency and reliability, reduced emissions, and reduced noise as compared to today's combustion-powered aircraft. This paper describes a novel flight demonstration concept that will enable the benefits of electric propulsion, while keeping the extraordinary convenience and utility of common fuels available at today's airports. A critical gap in airborne electric propulsion research is addressed by accommodating adoption at the integrated aircraft-airport systems level, using a confluence of innovative but proven concepts and technologies in power generation and electricity storage that need to reside only on the airframe. Technical discriminators of this demonstrator concept include (1) a novel, high-efficiency power system that utilizes advanced solid oxide fuel cells originally developed for ultra-long-endurance aircraft, coupled with (2) a high-efficiency, high-power electric propulsion system selected from mature products to reduce technical risk, assembled into (3) a modern, high-performance demonstration platform to provide useful and compelling data, both for the targeted early adopters and the eventual commercial market.

  18. From information theory to quantitative description of steric effects.

    PubMed

    Alipour, Mojtaba; Safari, Zahra

    2016-07-21

    Immense efforts have been made in the literature to apply the information theory descriptors for investigating the electronic structure theory of various systems. In the present study, the information theoretic quantities, such as Fisher information, Shannon entropy, Onicescu information energy, and Ghosh-Berkowitz-Parr entropy, have been used to present a quantitative description for one of the most widely used concepts in chemistry, namely the steric effects. Taking the experimental steric scales for the different compounds as benchmark sets, there are reasonable linear relationships between the experimental scales of the steric effects and theoretical values of steric energies calculated from information theory functionals. Perusing the results obtained from the information theoretic quantities with the two representations of electron density and shape function, the Shannon entropy has the best performance for the purpose. On the one hand, the usefulness of considering the contributions of functional groups steric energies and geometries, and on the other hand, dissecting the effects of both global and local information measures simultaneously have also been explored. Furthermore, the utility of the information functionals for the description of steric effects in several chemical transformations, such as electrophilic and nucleophilic reactions and host-guest chemistry, has been analyzed. The functionals of information theory correlate remarkably with the stability of systems and experimental scales. Overall, these findings show that the information theoretic quantities can be introduced as quantitative measures of steric effects and provide further evidences of the quality of information theory toward helping theoreticians and experimentalists to interpret different problems in real systems.

  19. Dynamics of Azobenzene Dimer Photoisomerization: Electronic and Steric Effects.

    PubMed

    Titov, Evgenii; Granucci, Giovanni; Götze, Jan Philipp; Persico, Maurizio; Saalfrank, Peter

    2016-09-15

    While azobenzenes readily photoswitch in solution, their photoisomerization in densely packed self-assembled monolayers (SAMs) can be suppressed. Reasons for this can be steric hindrance and/or electronic quenching, e.g., by exciton coupling. We address these possibilities by means of nonadiabatic molecular dynamics with trajectory surface hopping calculations, investigating the trans → cis isomerization of azobenzene after excitation into the ππ* absorption band. We consider a free monomer, an isolated dimer and a dimer embedded in a SAM-like environment of additional azobenzene molecules, imitating in this way the gradual transition from an unconstrained over an electronically coupled to an electronically coupled and sterically hindered, molecular switch. Our simulations reveal that in comparison to the single molecule the quantum yield of the trans → cis photoisomerization is similar for the isolated dimer, but greatly reduced in the sterically constrained situation. Other implications of dimerization and steric constraints are also discussed. PMID:27542538

  20. Overcoming: A Concept Analysis

    PubMed Central

    Brush, Barbara L.; Kirk, Keri; Gultekin, Laura; Baiardi, Janet M.

    2011-01-01

    This article provides an operational definition of overcoming as a first step in the systematic analysis of the concept. Using the method described by Walker and Avant (2005), the authors identify the attributes and characteristics of overcoming and its theoretical and practical application to nursing. Sample cases from clinical research illustrate the concept further. Further nursing research needs to test the theoretical relationships between overcoming and outcome variables. PMID:21806626

  1. Multidimensional steric parameters in the analysis of asymmetric catalytic reactions

    NASA Astrophysics Data System (ADS)

    Harper, Kaid C.; Bess, Elizabeth N.; Sigman, Matthew S.

    2012-05-01

    Although asymmetric catalysis is universally dependent on spatial interactions to impart specific chirality on a given substrate, examination of steric effects in these catalytic systems remains empirical. Previous efforts by our group and others have seen correlation between steric parameters developed by Charton and simple substituents in both substrate and ligand; however, more complex substituents were not found to be correlative. Here, we review and compare the steric parameters common in quantitative structure activity relationships (QSAR), a common method for pharmaceutical function optimization, and how they might be applied in asymmetric catalysis, as the two fields are undeniably similar. We re-evaluate steric/enantioselection relationships, which we previously analysed with Charton steric parameters, using the more sophisticated Sterimol parameters developed by Verloop and co-workers in a QSAR context. Use of these Sterimol parameters led to strong correlations in numerous processes where Charton parameters had previously failed. Sterimol parameterization also allows for greater mechanistic insight into the key elements of asymmetric induction within these systems.

  2. Understanding and Overcoming "Bottlenecks" in Student Learning

    ERIC Educational Resources Information Center

    Sturts, Jill R.; Mowatt, Rasul A.

    2012-01-01

    Pedagogically, the term "bottleneck" refers to a moment when students may face barriers to understanding content in the process of learning. As instructors identify "bottlenecks" within their courses, they are faced with the challenge of how to best assist students in overcoming them. Further, most instructors want to know what selected teaching…

  3. Overcoming breastfeeding problems

    MedlinePlus

    Plugged milk ducts; Nipple soreness when breastfeeding; Breastfeeding - overcoming problems; Let-down reflex ... oils can cause dry skin. Olive oil, expressed milk, and ointments containing lanolin can help soothe dry ...

  4. Sterically shielded diboron-containing metallocene olefin polymerization catalysts

    DOEpatents

    Marks, Tobin J.; Ja, Li; Yang, Xinmin

    1995-09-05

    A non-coordinating anion, preferably containing a sterically shielded diboron hydride, if combined with a cyclopenta-dienyl-substituted metallocene cation component, such as a zirconocene metallocene, is a useful olefin polymerization catalyst component. The anion preferably has the formula ##STR1## where R is branched lower alkyl, such as t-butyl.

  5. Steric effects in the chemisorption of vibrationally excited methane on Ni(100).

    PubMed

    Yoder, Bruce L; Bisson, Régis; Beck, Rainer D

    2010-07-30

    Newly available, powerful infrared laser sources enable the preparation of intense molecular beams of quantum-state prepared and aligned molecules for gas/surface reaction dynamics experiments. We present a stereodynamics study of the chemisorption of vibrationally excited methane on the (100) surface of nickel. Using linearly polarized infrared excitation of the C-H stretch modes of two methane isotopologues [CH4(nu3) and CD3H(nu1)], we aligned methane's angular momentum and vibrational transition dipole moment in the laboratory frame. An increase in methane reactivity of as much as 60% is observed when the laser polarization is parallel rather than normal to the surface. The dependence of the alignment effect on the rotational branch used for excitation indicates that alignment of the vibrational transition dipole moment of methane is responsible for the steric effect. Potential explanations for the steric effect in terms of an alignment-dependent reaction barrier height or electronically nonadiabatic effects are discussed. PMID:20671185

  6. Origin of anomeric effect: A density functional steric analysis

    SciTech Connect

    Huang, Ying; Zhong, Ai-Guo; Yang, Qinsong; Liu, Shubin

    2011-01-01

    The anomeric effect (the tendency of heteroatomic substituents adjacent to a heteroatom within the cyclohexane ring to prefer the axial orientation instead of the sterically less hindered equatorial position) is traditionally explained through either the dipole moment repulsion or the hyperconjugation effect. In this work, by employing our recent work in density functional steric analysis, we provide a novel two-component explanation, which is consistent with the common belief in chemistry that the effect has a stereoelectronic origin. With α-D-glucopyranose as the prototype, we systematically explore its conformational space and generate 32 isomers, leading to a total of 80 axial–equatorial conformation pairs. The energy difference analysis of these pairs shows that while statistically speaking the tendency is valid, the anomeric effect is not always true and can be violated. Three energy components, exchange–correlation, classical electrostatic, and density functional steric, are found to be directly proportional to the total energy difference between axial and equatorial isomers. We also found that the total dipole moment change, not the hyperconjugation effect, is a reasonable indicator of the total energy difference. However, all these correlations alone are not strong enough to provide a compellingly convincing explanation for the general validity of the effect. With the help of strong correlations between energy components, an explanation with two energy components, steric and electrostatic, was proposed in this work. We show that the axial–equatorial energy difference in general, with the anomeric effect as a special case, is dictated by two factors of the stereoelectronic origin, steric hindrance and classical electrostaticinteractions, synchronously working together. Another explanation in terms of exchange–correlation and electrostaticinteractions has also been obtained in this work.

  7. Overcoming recruitment barriers revealed high readiness to participate and low dropout rate among people with schizophrenia in a randomized controlled trial testing the effect of a Guided Self-Determination intervention

    PubMed Central

    2014-01-01

    Background Recruitment is one of the most serious challenges in performing randomized controlled trials. Often clinical trials with participants diagnosed with schizophrenia are terminated prematurely because of recruitment challenges resulting in a considerable waste of resources in the form of time, funding, and the participants’ efforts. Dropout rates in schizophrenia trials are also high. Recruitment challenges are often due to patients not wanting to participate in research but can also be due to clinicians’ concerns regarding individuals diagnosed with schizophrenia as participants in research. This paper reports how overcoming recruitment challenges not related to patients revealed high readiness to take part and low dropout rates in a one year long randomized controlled trial testing Guided Self-Determination (GSD) among outpatients with schizophrenia receiving treatment in Assertive Outreach Teams in the northern part of Denmark. Methods GSD is a shared decision-making and mutual problem-solving method using reflection sheets, which was developed in diabetes care and adjusted for this study and utilized by patients with schizophrenia. Descriptive data on strategies to overcome recruitment challenges were derived from notes and observations made during the randomized controlled trial testing of GSD in six outpatient teams. Results Three types of recruitment challenges not related to patients were identified and met during the trial: 1) organizational challenges, 2) challenges with finding eligible participants and 3) challenges with having professionals invite patients to participate. These challenges were overcome through: 1) extension of time, 2) expansion of the clinical recruitment area and 3) encouragement of professionals to invite patients to the study. Through overcoming these challenges, we identified a remarkably high patient-readiness to take part (101 of 120 asked accepted) and a low dropout rate (8%). Conclusion Distinction between

  8. Overcoming Passive Behavior.

    ERIC Educational Resources Information Center

    Kay, Marilyn

    1986-01-01

    Passivity in learning disabled children is identified as either inborn or as "learned helplessness," and the role of the teacher in overcoming passivity is noted. Teachers can help students understand themselves, become active agents in learning, and use self monitoring devices. (CL)

  9. Interactions of triazine herbicides with biochar: Steric and electronic effects.

    PubMed

    Xiao, Feng; Pignatello, Joseph J

    2015-09-01

    We studied the adsorption of triazine herbicides and several reference heteroaromatic amines from water onto a temperature series of hardwood biochars (300-700 °C, labeled B300-B700). Adsorption on biochars correlated poorly with pyrolysis temperature, H/C, O/C, mean minimum fused ring size, surface area (N2 or CO2), microporosity, and mesoporosity, but correlated well with a weighted sum of microporosity and mesoporosity. Steric effects were evident by the negative influence of solute molecular volume on adsorption rate. For a given compound, adsorption rate maximized for the biochar with the greatest mesoporosity-to-total-porosity ratio, suggesting that mesopores are important for facilitating diffusion into pore networks. The cationic forms of amines adsorb more slowly than the neutral forms. To further probe steric and electronic effects, adsorption on a biochar (B400) was compared to adsorption on graphite-a nonporous reference material with an unhindered, unfunctionalized graphene surface-and in comparison with reference compounds (benzene, naphthalene, pyridine, quinoline and 1,3-triazine). Relative to benzene, the surface area-normalized adsorption of the triazine herbicides was disfavored on B400 (favored on graphite) by 11-19 kJ/mol, depending on concentration. It is estimated that steric suppression of B400 adsorption comprises 6.2 kJ/mol of this difference, the remainder being the difference in polar electronic effects. Based on the behavior of the reference amines, the difference in polar effects is dominated by π-π electron donor-acceptor (EDA) interactions with sites on polyaromatic surfaces, which are more electropositive and/or more abundant on graphite. Overall, our results show that mesoporosity is critical, that adsorption rate is a function of solute molecular size and charge, that steric bulk in the solute suppresses equilibrium adsorption, and that π-π EDA forces play a role in triazine polar interactions with biochar. PMID:26001283

  10. Interactions of triazine herbicides with biochar: Steric and electronic effects.

    PubMed

    Xiao, Feng; Pignatello, Joseph J

    2015-09-01

    We studied the adsorption of triazine herbicides and several reference heteroaromatic amines from water onto a temperature series of hardwood biochars (300-700 °C, labeled B300-B700). Adsorption on biochars correlated poorly with pyrolysis temperature, H/C, O/C, mean minimum fused ring size, surface area (N2 or CO2), microporosity, and mesoporosity, but correlated well with a weighted sum of microporosity and mesoporosity. Steric effects were evident by the negative influence of solute molecular volume on adsorption rate. For a given compound, adsorption rate maximized for the biochar with the greatest mesoporosity-to-total-porosity ratio, suggesting that mesopores are important for facilitating diffusion into pore networks. The cationic forms of amines adsorb more slowly than the neutral forms. To further probe steric and electronic effects, adsorption on a biochar (B400) was compared to adsorption on graphite-a nonporous reference material with an unhindered, unfunctionalized graphene surface-and in comparison with reference compounds (benzene, naphthalene, pyridine, quinoline and 1,3-triazine). Relative to benzene, the surface area-normalized adsorption of the triazine herbicides was disfavored on B400 (favored on graphite) by 11-19 kJ/mol, depending on concentration. It is estimated that steric suppression of B400 adsorption comprises 6.2 kJ/mol of this difference, the remainder being the difference in polar electronic effects. Based on the behavior of the reference amines, the difference in polar effects is dominated by π-π electron donor-acceptor (EDA) interactions with sites on polyaromatic surfaces, which are more electropositive and/or more abundant on graphite. Overall, our results show that mesoporosity is critical, that adsorption rate is a function of solute molecular size and charge, that steric bulk in the solute suppresses equilibrium adsorption, and that π-π EDA forces play a role in triazine polar interactions with biochar.

  11. Steric interactions determine side-chain conformations in protein cores.

    PubMed

    Caballero, D; Virrueta, A; O'Hern, C S; Regan, L

    2016-09-01

    We investigate the role of steric interactions in defining side-chain conformations in protein cores. Previously, we explored the strengths and limitations of hard-sphere dipeptide models in defining sterically allowed side-chain conformations and recapitulating key features of the side-chain dihedral angle distributions observed in high-resolution protein structures. Here, we show that modeling residues in the context of a particular protein environment, with both intra- and inter-residue steric interactions, is sufficient to specify which of the allowed side-chain conformations is adopted. This model predicts 97% of the side-chain conformations of Leu, Ile, Val, Phe, Tyr, Trp and Thr core residues to within 20°. Although the hard-sphere dipeptide model predicts the observed side-chain dihedral angle distributions for both Thr and Ser, the model including the protein environment predicts side-chain conformations to within 20° for only 60% of core Ser residues. Thus, this approach can identify the amino acids for which hard-sphere interactions alone are sufficient and those for which additional interactions are necessary to accurately predict side-chain conformations in protein cores. We also show that our approach can predict alternate side-chain conformations of core residues, which are supported by the observed electron density.

  12. Steric Effects in the Reaction of Aryl Radicals on Surfaces

    SciTech Connect

    Combellas, Catherine; Jiang, Deen; Kanoufi, Frederic; Pinson, Jean; Podvorica, Fetah

    2009-01-01

    Steric effects are investigated in the reaction of aryl radicals with surfaces. The electrochemical reduction of 2-, 3-, 4-methyl, 2-methoxy, 2-ethyl, 2,6-, 2,4-, and 3,5-dimethyl, 4-tert-butyl, 3,5-bis-tert-butyl benzenediazonium, 3,5-bis(trifluoromethyl), and pentafluoro benzenediazonium tetrafluoroborates is examined in acetonitrile solutions. It leads to the formation of grafted layers only if the steric hindrance at the 2- or 2,6-position(s) is small. When the 3,5-positions are crowded with tert-butyl groups, the growth of the organic layer is limited by steric effects and a monolayer is formed. The efficiency of the grafting process is assessed by cyclic voltammetry, X-ray photoelectron spectroscopy, infrared, and ellipsometry. These experiments, together with density functional computations of bonding energies of substituted phenyl groups on a copper surface, are discussed in terms of the reactivity of aryl radicals in the electrografting reaction and in the growth of the polyaryl layer.

  13. Rotational, steric, and coriolis effects on the F + HCl --> HF + Cl reaction on the 1(2)A' ground-state surface.

    PubMed

    Defazio, Paolo; Petrongolo, Carlo

    2009-04-23

    We present a quantum study of the reaction F((2)P) + HCl(X(1)Sigma(+)) --> HF(X(1)Sigma(+)) + Cl((2)P) on a recently computed 1(2)A' ground-state surface, considering HCl in the ground vibrational state, with up to 16 rotational quanta j(0). We employ the real wavepacket (WP) and flux methods for calculating coupled-channel (CC) and centrifugal-sudden (CS) initial-state probabilities up to J = 80 and 140, respectively. We also report CC and CS ground-state cross sections and CS excited-state cross sections and discuss the dynamics analyzing WP time evolutions. The HCl rotation highly enhances reaction probabilities and cross sections, as it was previously found for probabilities at J Steric effects favor indeed the overcoming of the potential barrier and a linearly dominated mechanism. Attractive Coriolis couplings favor instead the energy flow from the HCl rotation to the F-H---Cl reactive vibration. WP snapshots confirm and explain the HCl rotational effects, because the density into the nearly collinear F-H---Cl product channel increases remarkably with j(0). Finally, our CS rate constant is underestimated with respect to the experiment, pointing out the need of more accurate multisurface and CC calculations.

  14. Cleanroom laboratory challenge overcome.

    PubMed

    Quinn, Ronan

    2010-10-01

    Ronan Quinn, managing director of interior construction specialist Ardmac, describes the challenges of building and fitting out a new cleanroom laboratory for blood and bone marrow therapeutic treatment at Our Lady's Children's Hospital Crumlin in Dublin. The "state-of-the-art" facility, which fully complies with the recent EU Directive concerning human tissues and cells, has been well received by the client and end-users alike, but, as he explains, there were many obstacles to overcome during its completion.

  15. Large steric effect in the substitution reaction of amines with phosphoimidazolide-activated nucleosides

    NASA Technical Reports Server (NTRS)

    Kanavarioti, A.; Stronach, M. W.; Ketner, R. J.; Hurley, T. B.

    1995-01-01

    Aliphatic amines react with phosphoimidazolide-activated derivatives of guanosine and cytidine (ImpN) by replacing the imidazole group. The kinetics of reaction of guanosine 5'-phospho-2-methylimidazolide (2-MeImpG) with glycine ethyl ester, glycinamide, 2-methoxyethylamine, n-butylamine, morpholine, dimethylamine (Me2NH), ethylmethylamine (EtNHMe), diethylamine (Et2NH), pyrrolidine, and piperidine were determined in water at 37 degrees C. With primary amines, a plot of the logarithm of the rate constant for attack by the amine on the protonated substrate, log kSH(A), versus the pKa of the amine exhibits a good linear correlation with a Bronsted slope, beta nuc = 0.48. Most of the secondary amines tested react with slightly higher reactivity than primary amines of similar pKa. Interestingly, some secondary amines show substantially lower reactivity than might be expected: EtNHMe reacts about eight times, and Et2NH at least 100 times, more slowly than Me2NH although all three amines are of similar basicity. For comparison, the kinetics of reaction of guanosine 5'-phosphoimidazolide (ImpG) and cytidine 5'-phosphoimidazolide (ImpC) were determined with Me2NH, EtNHMe, and Et2NH, and similar results were obtained. These results establish that the increased steric hindrance observed with the successive addition of ethyl groups are not due to any special steric requirements imposed by the guanosine or the methyl on the 2-methylimidazole leaving group of 2-MeImpG. It is concluded that addition of ethyl and, perhaps, groups larger than ethyl dramatically increases the kinetic barrier for addition of aliphatic secondary amines to the P-N bond of ImpN. This study supports the observation that the primary amino groups on the natural polyamines are at least 2 orders of magnitude more reactive than the secondary amino groups in the reaction with ImpN.

  16. Thin Filament Structure and the Steric Blocking Model.

    PubMed

    Lehman, William

    2016-04-01

    By interacting with the troponin-tropomyosin complex on myofibrillar thin filaments, Ca2+ and myosin govern the regulatory switching processes influencing contractile activity of mammalian cardiac and skeletal muscles. A possible explanation of the roles played by Ca2+ and myosin emerged in the early 1970s when a compelling "steric model" began to gain traction as a likely mechanism accounting for muscle regulation. In its most simple form, the model holds that, under the control of Ca2+ binding to troponin and myosin binding to actin, tropomyosin strands running along thin filaments either block myosin-binding sites on actin when muscles are relaxed or move away from them when muscles are activated. Evidence for the steric model was initially based on interpretation of subtle changes observed in X-ray fiber diffraction patterns of intact skeletal muscle preparations. Over the past 25 years, electron microscopy coupled with three-dimensional reconstruction directly resolved thin filament organization under many experimental conditions and at increasingly higher resolution. At low-Ca2+, tropomyosin was shown to occupy a "blocked-state" position on the filament, and switched-on in a two-step process, involving first a movement of tropomyosin away from the majority of the myosin-binding site as Ca2+ binds to troponin and then a further movement to fully expose the site when small numbers of myosin heads bind to actin. In this contribution, basic information on Ca2+-regulation of muscle contraction is provided. A description is then given relating the voyage of discovery taken to arrive at the present understanding of the steric regulatory model. PMID:27065174

  17. Optimized steric stabilization of aqueous ferrofluids and magnetic nanoparticles.

    PubMed

    Jain, Nirmesh; Wang, Yanjun; Jones, Stephen K; Hawkett, Brian S; Warr, Gregory G

    2010-03-16

    The preparation and properties of an aqueous ferrofluid consisting of a concentrated (>65 wt %) dispersion of sterically stabilized superparamagnetic, iron oxide (maghemite) nanoparticles stable for several months at high ionic strength and over a broad pH range is described. The 6-8 nm diameter nanoparticles are individually coated with a short poly(acrylic acid)-b-poly(acrylamide) copolymer, designed to form the thinnest possible steric stabilizing layer while remaining strongly attached to the iron oxide surface over a wide range of nanoparticle concentrations. Thermogravimetric analysis yields an iron oxide content of 76 wt % in the dried particles, consistent with a dry polymer coating of approximately 1 nm in thickness, while the poly(acrylamide) chain length indicated by electrospray mass spectrometry is consistent with the 4-5 nm increase in the hydrodynamic radius observed by light scattering when the poly(acrylamide) stabilizing chains are solvated. Saturation magnetization experiments indicate nonmagnetic surface layers resulting from the strong chemical attachment of the poly(acrylic acid) block to the particle surface, also observed by Fourier transform infrared spectroscopy. PMID:19950943

  18. Overcoming associative learning.

    PubMed

    Haselgrove, Mark

    2016-08-01

    Thorndike (1898, 1911) rejected the idea that animal behavior was the consequence of reasoning, and suggested instead that the gradual acquisition of associations formed the basis of behavior-a contention that has had a significant impact on the development of animal learning theory. Despite this, comparative psychology provides a number of examples of behaviors that have been considered to be above and beyond the explanation of associative-, or reinforcement-learning mechanisms. These behaviors have motivated some researchers to propose higher-order cognitive abilities in animals, including (but not limited to) reasoning, sensitivity to ambiguity, and metacognition. However, other authors have questioned this claim, and provided alternative explanations for these behaviors from an associative perspective. With relevant examples, the steps that must be taken in order to overcome an associative explanation of behavior are described. (PsycINFO Database Record PMID:26986019

  19. Overcoming associative learning.

    PubMed

    Haselgrove, Mark

    2016-08-01

    Thorndike (1898, 1911) rejected the idea that animal behavior was the consequence of reasoning, and suggested instead that the gradual acquisition of associations formed the basis of behavior-a contention that has had a significant impact on the development of animal learning theory. Despite this, comparative psychology provides a number of examples of behaviors that have been considered to be above and beyond the explanation of associative-, or reinforcement-learning mechanisms. These behaviors have motivated some researchers to propose higher-order cognitive abilities in animals, including (but not limited to) reasoning, sensitivity to ambiguity, and metacognition. However, other authors have questioned this claim, and provided alternative explanations for these behaviors from an associative perspective. With relevant examples, the steps that must be taken in order to overcome an associative explanation of behavior are described. (PsycINFO Database Record

  20. Barriers to improvements in energy efficiency

    SciTech Connect

    Reddy, A.K.N.

    1991-10-01

    To promote energy-efficiency improvements, actions may be required at one or more levels -- from the lowest level of the consumer (residential, commercial, industrial, etc.) through the highest level of the global agencies. But barriers to the implementation of energy-efficiency improvements exist or can arise at all these levels. Taking up each one of these barriers in turn, the paper discusses specific measures that can contribute to overcoming the barriers. However, a one-barrier-one-measure approach must be avoided. Single barriers may in fact involve several sub-barriers. Also, combinations of measures are much more effective in overcoming barriers. In particular, combinations of measures that simultaneously overcome several barriers are most successful. The paper discusses the typology of barriers, explores their origin and suggests measures that by themselves or in combination with other measures, will overcome these barriers. Since most of the barriers dealt with can be found in the barriers'' literature, any originality in the paper lies in its systematic organization, synoptic view and holistic treatment of this issue. This paper is intended to initiate a comprehensive treatment of barriers, their origins and the measures that contribute to overcoming them. Hopefully, such a treatment will facilitate the implementation of energy-efficiency improvements involving a wide diversity of ever-changing energy end uses and consumer preferences.

  1. Barriers to improvements in energy efficiency

    SciTech Connect

    Reddy, A.K.N.

    1991-10-01

    To promote energy-efficiency improvements, actions may be required at one or more levels -- from the lowest level of the consumer (residential, commercial, industrial, etc.) through the highest level of the global agencies. But barriers to the implementation of energy-efficiency improvements exist or can arise at all these levels. Taking up each one of these barriers in turn, the paper discusses specific measures that can contribute to overcoming the barriers. However, a one-barrier-one-measure approach must be avoided. Single barriers may in fact involve several sub-barriers. Also, combinations of measures are much more effective in overcoming barriers. In particular, combinations of measures that simultaneously overcome several barriers are most successful. The paper discusses the typology of barriers, explores their origin and suggests measures that by themselves or in combination with other measures, will overcome these barriers. Since most of the barriers dealt with can be found in the ``barriers`` literature, any originality in the paper lies in its systematic organization, synoptic view and holistic treatment of this issue. This paper is intended to initiate a comprehensive treatment of barriers, their origins and the measures that contribute to overcoming them. Hopefully, such a treatment will facilitate the implementation of energy-efficiency improvements involving a wide diversity of ever-changing energy end uses and consumer preferences.

  2. Modulations in restricted amide rotation by steric induced conformational trapping

    NASA Astrophysics Data System (ADS)

    Krishnan, V. V.; Thompson, William B.; Goto, Joy J.; Maitra, Kalyani; Maitra, Santanu

    2012-01-01

    The rotation around the amide bond in N,N-diethyl-m-toluamide (m-DEET) has been studied extensively and often used in laboratory instructions to demonstrate the phenomenon of chemical exchange. Herein, we show that a simple modification to N,N-diethyl-o-toluamide (o-DEET) significantly alters the dynamics of the restricted rotation around the amide bond due to steric interactions between the ring methyl group and the two N-ethyl groups. This alters the classic two-site exchange due to restricted rotation around the amide bond, to a three-site exchange, with the third conformation trapped at a higher-energy state compared to the other two. This often overlooked phenomenon is elucidated using variable-temperature NMR, two-dimensional exchange spectroscopy and molecular modeling studies.

  3. A combinatorial approach to producing sterically stabilized (Stealth) immunoliposomal drugs.

    PubMed

    Ishida, T; Iden, D L; Allen, T M

    1999-10-22

    We have developed a method for producing sterically stabilized immunoliposomal drugs (SIL) readily applicable to a 'mix and match' combinatorial approach for the simple manufacture of a variety of ligand-targeted liposomal drugs. Ligands coupled to the terminus of polyethylene glycol (PEG) in micelles formed from PEG-lipid derivatives (mPEG2000-DSPE) could be transferred into preformed, drug-containing liposomes from the micelles in a temperature- and time-dependent manner. Antibody densities up to 100 microg antibody/micromol of phospholipid, and up to 3 mol% of mPEG2000-DSPE, could be simultaneously transferred from the ligand-coupled micelles into the liposomal outer monolayer with negligible drug leakage from liposomes during transfer and good stability in human plasma. Transfer of anti-CD19 into SIL resulted in a three-fold increase in binding of these liposomes to CD19+ human B cell lymphoma cells.

  4. SAXS Study of Sterically Stabilized Lipid Nanocarriers Functionalized by DNA

    NASA Astrophysics Data System (ADS)

    Angelov, Borislav; Angelova, Angelina; Filippov, Sergey; Karlsson, Göran; Terrill, Nick; Lesieur, Sylviane; Štěpánek, Petr

    2012-03-01

    The structure of novel spontaneously self-assembled plasmid DNA/lipid complexes is investigated by means of synchrotron radiation small-angle X-ray scattering (SAXS) and Cryo-TEM imaging. Liquid crystalline (LC) hydrated lipid systems are prepared using the non-ionic lipids monoolein and DOPE-PEG2000 and the cationic amphiphile CTAB. The employed plasmid DNA (pDNA) is encoding for the human protein brain-derived neurotrophic factor (BDNF). A coexistence of nanoparticulate objects with different LC inner organizations is established. A transition from bicontinuous membrane sponges, cubosome intermediates and unilamelar liposomes to multilamellar vesicles, functionalized by pDNA, is favoured upon binding and compaction of pBDNF onto the cationic PEGylated lipid nanocarriers. The obtained sterically stabilized multicompartment nanoobjects, with confined supercoiled plasmid DNA (pBDNF), are important in the context of multicompartment lipid nanocarriers of interest for gene therapy of neurodegenerative diseases.

  5. Lis1 regulates dynein by sterically blocking its mechanochemical cycle.

    PubMed

    Toropova, Katerina; Zou, Sirui; Roberts, Anthony J; Redwine, William B; Goodman, Brian S; Reck-Peterson, Samara L; Leschziner, Andres E

    2014-11-07

    Regulation of cytoplasmic dynein's motor activity is essential for diverse eukaryotic functions, including cell division, intracellular transport, and brain development. The dynein regulator Lis1 is known to keep dynein bound to microtubules; however, how this is accomplished mechanistically remains unknown. We have used three-dimensional electron microscopy, single-molecule imaging, biochemistry, and in vivo assays to help establish this mechanism. The three-dimensional structure of the dynein-Lis1 complex shows that binding of Lis1 to dynein's AAA+ ring sterically prevents dynein's main mechanical element, the 'linker', from completing its normal conformational cycle. Single-molecule experiments show that eliminating this block by shortening the linker to a point where it can physically bypass Lis1 renders single dynein motors insensitive to regulation by Lis1. Our data reveal that Lis1 keeps dynein in a persistent microtubule-bound state by directly blocking the progression of its mechanochemical cycle.

  6. Blocking cyclobutane pyrimidine dimer formation by steric hindrance.

    PubMed

    Vendrell-Criado, Victoria; Lhiaubet-Vallet, Virginie; Yamaji, Minoru; Cuquerella, M Consuelo; Miranda, Miguel A

    2016-04-26

    The efficiency of thymine (Thy) and uracil (Ura) to form cyclobutane pyrimidine dimers (CPDs) in solution, upon UV irradiation differs by one order of magnitude. This could to be partially related to the steric hindrance induced by the methyl at C5 in thymine. The aim of the present work is to establish the influence of a bulky moiety at this position on the photoreactivity of pyrimidines. With this purpose, photosensitization with benzophenone and acetone of a 5-tert-butyl uracil derivative () and the equivalent Thy () has been compared. Introduction of the tert-butyl group completely blocks CPD formation. Moreover, the mechanistic insight obtained by laser flash photolysis is in accordance with the observed photoreactivity. PMID:27112630

  7. Steric effects and preferential interactions in supercritical carbon dioxide

    SciTech Connect

    Saquing, C.D.; Lucien, F.P.; Foster, N.R

    1998-10-01

    Solubility data are presented for a mixture of o-hydroxybenzoic acid (o-HBA) and m-HBA in supercritical CO{sub 2} doped with 3.5 mol% methanol. The data were measured at 318 and 328 K and for pressures in the range of 101--201 bar. Some new data for the solubility of pure m-HBA in methanol-doped supercritical CO{sub 2} are also presented. The solubilities of the HBA isomers are enhanced considerably with the addition of methanol to supercritical CO{sub 2}. However, the solubility enhancement is strongly affected by the spatial arrangement of their functional groups (steric effect). There appears to be preferential interaction between the solutes and the cosolvent in the quaternary system, and this phenomenon is consistent with thermodynamic modeling of the system.

  8. Steric-electronic effects in malarial peptides inducing sterile immunity

    SciTech Connect

    Moreno-Vranich, Armando; Patarroyo, Manuel E.

    2012-07-13

    Highlights: Black-Right-Pointing-Pointer Is it evident that the residues position are relevant regarding of {phi} angular value. Black-Right-Pointing-Pointer The geometry considered for detailing the alterations undergone by HABPs. Black-Right-Pointing-Pointer The inter planar interactions ruled by clashes between the atoms making them up. -- Abstract: Conserved Plasmodium falciparum high activity binding peptides' (HABPs) most relevant proteins involved in malaria parasite invasion are immunologically silent; critical binding residues must therefore be specifically replaced to render them highly immunogenic and protection-inducing. Such changes have a tremendous impact on these peptides' steric-electronic effects, such as modifications to peptide length peptide bonds and electronic orbitals' disposition, to allow a better fit into immune system MHCII molecules and better interaction with the TCR which might account for the final immunological outcome.

  9. Sterically stabilized water based magnetic fluids: Synthesis, structure and properties

    NASA Astrophysics Data System (ADS)

    Bica, Doina; Vékás, Ladislau; Avdeev, Mikhail V.; Marinică, Oana; Socoliuc, Vlad; Bălăsoiu, Maria; Garamus, Vasil M.

    2007-04-01

    Magnetic fluids (MFs), prepared by chemical co-precipitation followed by double layer steric and electrostatic (combined) stabilization of magnetite nanoparticles dispersed in water, are presented. Several combinations of surfactants with different chain lengths (lauric acid (LA), myristic acid (MA), oleic acid (OA) and dodecyl-benzene-sulphonic acid (DBS)) were used, such as LA+LA, MA+MA, LA+DBS, MA+DBS, OA+DBS, OA+OA and DBS+DBS. Static light scattering, transmission electron microscopy, small angle neutron scattering, magnetic and magneto-rheological measurements revealed that MFs with MA+MA or LA+LA biocompatible double layer covered magnetite nanoparticles are the most stable colloidal systems among the investigated samples, and thus suitable for biomedical applications.

  10. Steric and Electronic Effects of Bidentate Phosphine Ligands on Ruthenium(II)-Catalyzed Hydrogenation of Carbon Dioxide.

    PubMed

    Zhang, Pan; Ni, Shao-Fei; Dang, Li

    2016-09-20

    The reactivity difference between the hydrogenation of CO2 catalyzed by various ruthenium bidentate phosphine complexes was explored by DFT. In addition to the ligand dmpe (Me2 PCH2 CH2 PMe2 ), which was studied experimentally previously, a more bulky diphosphine ligand, dmpp (Me2 PCH2 CH2 CH2 PMe2 ), together with a more electron-withdrawing diphosphine ligand, PN(Me) P (Me2 PCH2 N(Me) CH2 PMe2 ), have been studied theoretically to analyze the steric and electronic effects on these catalyzed reactions. Results show that all of the most favorable pathways for the hydrogenation of CO2 catalyzed by bidentate phosphine ruthenium dihydride complexes undergo three major steps: cis-trans isomerization of ruthenium dihydride complex, CO2 insertion into the Ru-H bond, and H2 insertion into the ruthenium formate ion. Of these steps, CO2 insertion into the Ru-H bond has the lowest barrier compared with the other two steps in each preferred pathway. For the hydrogenation of CO2 catalyzed by ruthenium complexes of dmpe and dmpp, cis-trans isomerization of ruthenium dihydride complex has a similar barrier to that of H2 insertion into the ruthenium formate ion. However, in the reaction catalyzed by the PN(Me) PRu complex, cis-trans isomerization of the ruthenium dihydride complex has a lower barrier than H2 insertion into the ruthenium formate ion. These results suggest that the steric effect caused by the change of the outer sphere of the diphosphine ligand on the reaction is not clear, although the electronic effect is significant to cis-trans isomerization and H2 insertion. This finding refreshes understanding of the mechanism and provides necessary insights for ligand design in transition-metal-catalyzed CO2 transformation. PMID:27500596

  11. Steric spacing of molecular linkers on passivated Si(111) photoelectrodes.

    PubMed

    Li, Feng; Basile, Victoria M; Pekarek, Ryan T; Rose, Michael J

    2014-11-26

    Surfaces with high photoelectrochemical and electronic quality can be prepared by tethering small molecules to single-crystalline Si(111) surfaces using a two-step halogenation/alkylation method (by Lewis and co-workers).1-7 We report here that the surface coverage of custom-synthesized, phenyl-based molecular linkers can be controlled by varying the steric size of R-groups (R=CH3, C6H11, 2-ethylhexyl) at the periphery of the linker. Additionally, the linkers possess a para triflate group (-O2SCF3) that serves as a convenient analytical marker and as a point of covalent attachment for a redox active label. Quantitative X-ray photoelectron spectroscopy (XPS) measurements revealed that the surface coverage systematically varies according to the steric size of the linker: CH3 (6.7±0.8%), CyHex (2.9±1.2%), EtHex (2.1±0.9%). The stability of the photoelectrochemical cyclic voltammetry (PEC-CV) behavior was dependent on an additional methylation step (with CH3MgCl) to passivate residual Si(111)-Cl bonds. Subsequently, the triflate functional group was utilized to perform Pd-catalyzed Heck coupling of vinylferrocene to the surface-attached linkers. Ferrocene surface coverages measured from cyclic voltammetry on the ferrocene-functionalized surfaces Si(111)-8a/CH3-Fc (R=CH3) and Si(111)-8c/CH3-Fc (R=2-EtHex) are consistent with the corresponding Fe 2p XPS coverages and suggest a ∼1:1 conversion of surface triflate groups to vinyl-Fc sites. The surface defect densities of the linker/CH3 modified surfaces are dependent on the coverage and composition of the organic layer. Surface recombination velocity (SRV) measurements indicated that n-Si(111)-8a/CH3 and the ferrocene coupled n-Si(111)-8a/CH3-Fc exhibited relatively high surface carrier lifetimes (4.51 and 3.88 μs, respectively) and correspondingly low S values (3880 and 4510 cm s(-1)). Thus, the multistep, linker/Fc functionalized surfaces exhibit analogously low trap state densities as compared to the fully

  12. Nano- and microfabrication for overcoming drug delivery challenges

    PubMed Central

    Kam, Kimberly R.

    2013-01-01

    This highlight article describes current nano- and microfabrication techniques for creating drug delivery devices. We first review the main physiological barriers to delivering therapeutic agents. Then, we describe how novel fabrication methods can be utilized to combine many features into a single physiologically relevant device to overcome drug delivery challenges. PMID:23730504

  13. Mid-Atlantic Wind - Overcoming the Challenges

    SciTech Connect

    Daniel F. Ancona III; Kathryn E. George; Richard P. Bowers; Dr. Lynn Sparling; Bruce Buckheit; Daniel LoBue

    2012-05-31

    This study, supported by the US Department of Energy, Wind Powering America Program, Maryland Department of Natural Resources and Chesapeake Bay Foundation, analyzed barriers to wind energy development in the Mid-Atlantic region along with options for overcoming or mitigating them. The Mid-Atlantic States including Delaware, Maryland, North Carolina and Virginia, have excellent wind energy potential and growing demand for electricity, but only two utility-scale projects have been installed to date. Reasons for this apathetic development of wind resources were analyzed and quantified for four markets. Specific applications are: 1) Appalachian mountain ridgeline sites, 2) on coastal plains and peninsulas, 3) at shallow water sites in Delaware and Chesapeake Bays, Albemarle and Pamlico Sounds, and 4) at deeper water sites off the Atlantic coast. Each market has distinctly different opportunities and barriers. The primary barriers to wind development described in this report can be grouped into four categories; state policy and regulatory issues, wind resource technical uncertainty, economic viability, and public interest in environmental issues. The properties of these typologies are not mutually independent and do interact. The report concluded that there are no insurmountable barriers to land-based wind energy projects and they could be economically viable today. Likewise potential sites in sheltered shallow waters in regional bay and sounds have been largely overlooked but could be viable currently. Offshore ocean-based applications face higher costs and technical and wind resource uncertainties. The ongoing research and development program, revision of state incentive policies, additional wind measurement efforts, transmission system expansion, environmental baseline studies and outreach to private developers and stakeholders are needed to reduce barriers to wind energy development.

  14. Mid-Atlantic Wind - Overcoming the Challenges

    SciTech Connect

    Daniel F. Ancona III; Kathryn E. George; Lynn Sparling; Bruce C. Buckheit; Daniel LoBue; and Richard P. Bowers

    2012-06-29

    This study, supported by the US Department of Energy, Wind Powering America Program, Maryland Department of Natural Resources and Chesapeake Bay Foundation, analyzed barriers to wind energy development in the Mid-Atlantic region along with options for overcoming or mitigating them. The Mid-Atlantic States including Delaware, Maryland, North Carolina and Virginia, have excellent wind energy potential and growing demand for electricity, but only two utility-scale projects have been installed to date. Reasons for this apathetic development of wind resources were analyzed and quantified for four markets. Specific applications are: 1) Appalachian mountain ridgeline sites, 2) on coastal plains and peninsulas, 3) at shallow water sites in Delaware and Chesapeake Bays, Albemarle and Pamlico Sounds, and 4) at deeper water sites off the Atlantic coast. Each market has distinctly different opportunities and barriers. The primary barriers to wind development described in this report can be grouped into four categories; state policy and regulatory issues, wind resource technical uncertainty, economic viability, and public interest in environmental issues. The properties of these typologies are not mutually independent and do interact. The report concluded that there are no insurmountable barriers to land-based wind energy projects and they could be economically viable today. Likewise potential sites in sheltered shallow waters in regional bay and sounds have been largely overlooked but could be viable currently. Offshore ocean-based applications face higher costs and technical and wind resource uncertainties. The ongoing research and development program, revision of state incentive policies, additional wind measurement efforts, transmission system expansion, environmental baseline studies and outreach to private developers and stakeholders are needed to reduce barriers to wind energy development.

  15. Overcoming cellular and tissue barriers to improve liposomal drug delivery

    NASA Astrophysics Data System (ADS)

    Kohli, Aditya G.

    Forty years of liposome research have demonstrated that the anti-tumor efficacy of liposomal therapies is, in part, driven by three parameters: 1) liposome formulation and lipid biophysics, 2) accumulation and distribution in the tumor, and 3) release of the payload at the site of interest. This thesis outlines three studies that improve on each of these delivery steps. In the first study, we engineer a novel class of zwitterlipids with an inverted headgroup architecture that have remarkable biophysical properties and may be useful for drug delivery applications. After intravenous administration, liposomes accumulate in the tumor by the enhanced permeability and retention effect. However, the tumor stroma often limits liposome efficacy by preventing distribution into the tumor. In the second study, we demonstrate that depletion of hyaluronan in the tumor stroma improves the distribution and efficacy of DoxilRTM in murine 4T1 tumors. Once a liposome has distributed to the therapeutic site, it must release its payload over the correct timescale. Few facile methods exist to quantify the release of liposome therapeutics in vivo. In the third study, we outline and validate a simple, robust, and quantitative method for tracking the rate and extent of release of liposome contents in vivo. This tool should facilitate a better understanding of the pharmacodynamics of liposome-encapsulated drugs in animals. This work highlights aspects of liposome behavior that have prevented successful clinical translation and proposes alternative approaches to improve liposome drug delivery.

  16. Overcoming Barriers: Engaging Younger Students in an Online Intercultural Exchange

    ERIC Educational Resources Information Center

    Peiser, Gillian

    2015-01-01

    This paper reports on a small-scale project involving an online school exchange between two classes of 12-/13-year olds located in the North of England and the Ruhr area of Germany. The overarching aim of the project was to develop intercultural understanding in foreign language learning through communication in an online environment. Analysing…

  17. Postsecondary Correctional Education: Recognizing and Overcoming Barriers to Success

    ERIC Educational Resources Information Center

    Palmer, Shelby M.

    2012-01-01

    Postsecondary programs offering vocational training and college credit to eligible inmates have had difficulty finding a place in the U.S. correctional system. Politically motivated restrictions preventing inmates from receiving federal funds for college resulted in drastic program closures. Although new laws restored funding to select inmates,…

  18. Overcoming the Financial Aid Barrier for E-Learners

    ERIC Educational Resources Information Center

    Chaloux, Bruce

    2008-01-01

    Financial aid systems help make higher education available to all who can benefit. To "adjust" the existing financial aid system to make it more student friendly and open doors currently closed to many part-time learners and students with the greatest financial challenges, state policy changes and greater private sector initiatives targeted at…

  19. Overcoming Barriers for "Niche" Learners through Distance Learning.

    ERIC Educational Resources Information Center

    Miller, Lawrence G.; And Others

    For over 15 years, Tennessee's Chattanooga State Technical Community College has been offering non-traditional, distance education to reach "niches" of students who would otherwise find it difficult to attain a college education. Begun in 1979 with a laboratory-based independent study program offering a mix of purchased and locally-developed…

  20. Overcoming Barriers to Intercultural Relationships: A Culturally Competent Approach.

    ERIC Educational Resources Information Center

    Osher, David; Mejia, Brenda

    1999-01-01

    Profiles programs of two youth centers that are successfully bridging cultural differences through the development of cultural competence. Both centers acknowledge that actualizing cross-cultural competency means providing a way for their ethnic groups to interact with the larger population without losing their cultural heritage. Programs include…

  1. Improving The Perfect Storm: Overcoming Barriers To Climate Literacy

    NASA Astrophysics Data System (ADS)

    Tillinger, D.

    2015-12-01

    Students and scientists are trained to speak different languages. Climate science, and the geosciences more broadly, are strictly classroom topics, not subjects appropriate for casual conversation, social media, or creative projects. When students are aware of climate change through the mainstream media, it is nearly always in a political or technological context rather than a scientific one. However, given the opportunity, students are perfectly capable of not only understanding the science behind climate change, but communicating it to their peers. At the American Museum of Natural History, a group of underprivileged high school students visited Nature's Fury: The Science of Natural Disasters to learn about volcanoes, earthquakes, and climate change impacts. They were then able to write pitches and develop trailers for scientifically accurate, but still compelling, disaster movies. Arts in Parts, a creative outreach group formed as a response to Hurricane Sandy, facilitated a workshop in which younger children made mobiles from beach debris they collected while learning about the the threat of sea level rise locally and globally. Participants in an undergraduate natural disasters class wrote guides to understanding climate change that remained factual while showing great creativity and reflecting the personality of each student. Art, humor, and popular culture are the languages that society chooses to use; scientific literacy might benefit from their inclusion.

  2. What Changes Education? An Action Research to Overcome Barriers

    ERIC Educational Resources Information Center

    Eskicioglu, Yeser Eroglu

    2016-01-01

    According to the National Disabled People Data Base within Ministry of Family and Social Policies (Özveri), there are 1.559.222 disabled people in Turkey. If this rate would be linked to the families of the disabled people, the number of people who spend time with disabled individuals would increase to 10 million. This number corresponds to 12.5%…

  3. Wind Power in Australia: Overcoming Technological and Institutional Barriers

    ERIC Educational Resources Information Center

    Healey, Gerard; Bunting, Andrea

    2008-01-01

    Until recently, Australia had little installed wind capacity, although there had been many investigations into its potential during the preceding decades. Formerly, state-owned monopoly utilities showed only token interest in wind power and could dictate the terms of energy debates. This situation changed in the late 1990s: Installed wind capacity…

  4. Telecollaborative Networks in University Higher Education: Overcoming Barriers to Integration

    ERIC Educational Resources Information Center

    O'Dowd, Robert

    2013-01-01

    Foreign language telecollaboration refers to virtual intercultural interaction and exchange projects between classes of learners in geographically distant locations. While research findings on telecollaboration have confirmed its valuable contribution to students' foreign language, intercultural and electronic competences, a preliminary research…

  5. Overcoming Barriers for "Niche" Learners Through Distance Education.

    ERIC Educational Resources Information Center

    Miller, Lawrence G.; Hyatt, Sue Y.; Brennan, Joyce; Bertani, Raymond; Trevor, Thomas

    1999-01-01

    Focuses on students who fit into "niches," and discusses how the Chattanooga State Technical Community College's distance-learning program accommodates these learners. Describes five "niche" learner categories: students with disabilities, power-line maintenance technicians, emergency-service personnel, truckers, and industrial maintenance workers…

  6. Acceleration: Overcoming the Vector Barrier with Simple Practical Models.

    ERIC Educational Resources Information Center

    Whitworth, R.

    1988-01-01

    Describes five basic concepts, such as displacement, velocity, momentum, force, and moment of force. Discusses an experimental model to improve the intuitive understanding of acceleration in a straight line and a non-linear situation. (YP)

  7. Overcoming the Database Vocabulary Barrier--A Solution.

    ERIC Educational Resources Information Center

    And Others; Niehoff, Robert

    1979-01-01

    Discusses the Vocabulary Switching System (VSS), an experimental, automated switching system, which specifically addresses the problems of heterogeneous database vocabularies and indexes and the difficulty these pose for users who wish to combine more than one database in a single online search. (CWM)

  8. CAI: Overcoming Attitude Barriers of Prospective Primary Teachers. Final Report.

    ERIC Educational Resources Information Center

    Kockler, Lois H.

    During each of two school quarters, approximately 60 college students enrolled in a mathematics course were randomly assigned to an experimental group or a control group. The control group received instruction by the lecture method only; the experimental group received the same instruction, except that six computer-assisted instruction (CAI) units…

  9. Enhanced Amendment Delivery to Overcome Subsurface Physical Remediation Barriers

    NASA Astrophysics Data System (ADS)

    Zhong, L.; Truex, M. J.; Oostrom, M.; Szecsody, J. E.; Vermeul, V.; Li, X.

    2013-12-01

    Waste discharges can result in contamination of the unsaturated zone (vadose zone) and the water saturated zone (aquifer). To restore the environment, many in situ remediation technologies rely on delivery of remedial reagents (amendments) to the subsurface that treat or help remove contamination. However, through numerous remediation applications, the remediation industry has recognized that a major issue with in situ remediation is the difficulty in achieving an even spatial distribution of remedial amendments to the contamination zones in an aquifer or in the vadose zone. Poor amendment delivery leads to ineffective environmental restoration because some of the contaminants are not contacted by the amendment and, therefore, not treated or removed. This challenge often leads to a failure in environment restoration. Researches are being conducted to develop enhanced remediation amendment delivery approaches using shear thinning fluids (STFs) for aquifer and aqueous foams for vadose zone. STFs have properties that promote more uniform delivery of injected solutions so that amendments are able to reach low-permeability zones in an aquifer. These low-permeability zones are most difficult to reach with conventional delivery approaches, yet often contain the high contamination concentrations. Foam delivery is targeted for distribution of aqueous, gaseous amendments, and remedial nano-particles to the vadose zone. Foam transport in the vadose zone provides significant advantages for lateral distribution of amendments compared to aqueous-phase transport, improves uniformity of distribution compared to both aqueous- and gas-phase injection, and enables delivery of a broader range of remediation amendments than can be delivered in the gas phase.

  10. Modulated nematic structures induced by chirality and steric polarization

    NASA Astrophysics Data System (ADS)

    Longa, Lech; PajÄ k, Grzegorz

    2016-04-01

    What kind of one-dimensional modulated nematic structures (ODMNS) can form nonchiral and chiral bent-core and dimeric materials? Here, using the Landau-de Gennes theory of nematics, extended to account for molecular steric polarization, we study a possibility of formation of ODMNS, both in nonchiral and intrinsically chiral liquid crystalline materials. Besides nematic and cholesteric phases, we find four bulk ODMNS for nonchiral materials, two of which, to the best of our knowledge, have not been reported so far. These two structures are longitudinal (NLP) and transverse (NTP) periodic waves where the polarization field being periodic in one dimension stays parallel and perpendicular, respectively, to the wave vector. The other two phases are the twist-bend nematic phase (NTB) and the splay-bend nematic phase (NSB), but their fine structure appears more complex than that considered so far. The presence of molecular chirality converts nonchiral NTP and NSB into new NTB phases. Surprisingly, the nonchiral NLP phase can stay stable even in the presence of intrinsic chirality.

  11. Lis1 regulates dynein by sterically blocking its mechanochemical cycle

    PubMed Central

    Toropova, Katerina; Zou, Sirui; Roberts, Anthony J; Redwine, William B; Goodman, Brian S; Reck-Peterson, Samara L; Leschziner, Andres E

    2014-01-01

    Regulation of cytoplasmic dynein's motor activity is essential for diverse eukaryotic functions, including cell division, intracellular transport, and brain development. The dynein regulator Lis1 is known to keep dynein bound to microtubules; however, how this is accomplished mechanistically remains unknown. We have used three-dimensional electron microscopy, single-molecule imaging, biochemistry, and in vivo assays to help establish this mechanism. The three-dimensional structure of the dynein–Lis1 complex shows that binding of Lis1 to dynein's AAA+ ring sterically prevents dynein's main mechanical element, the ‘linker’, from completing its normal conformational cycle. Single-molecule experiments show that eliminating this block by shortening the linker to a point where it can physically bypass Lis1 renders single dynein motors insensitive to regulation by Lis1. Our data reveal that Lis1 keeps dynein in a persistent microtubule-bound state by directly blocking the progression of its mechanochemical cycle. DOI: http://dx.doi.org/10.7554/eLife.03372.001 PMID:25380312

  12. Modulated nematic structures induced by chirality and steric polarization.

    PubMed

    Longa, Lech; Pająk, Grzegorz

    2016-04-01

    What kind of one-dimensional modulated nematic structures (ODMNS) can form nonchiral and chiral bent-core and dimeric materials? Here, using the Landau-de Gennes theory of nematics, extended to account for molecular steric polarization, we study a possibility of formation of ODMNS, both in nonchiral and intrinsically chiral liquid crystalline materials. Besides nematic and cholesteric phases, we find four bulk ODMNS for nonchiral materials, two of which, to the best of our knowledge, have not been reported so far. These two structures are longitudinal (N_{LP}) and transverse (N_{TP}) periodic waves where the polarization field being periodic in one dimension stays parallel and perpendicular, respectively, to the wave vector. The other two phases are the twist-bend nematic phase (N_{TB}) and the splay-bend nematic phase (N_{SB}), but their fine structure appears more complex than that considered so far. The presence of molecular chirality converts nonchiral N_{TP} and N_{SB} into new N_{TB} phases. Surprisingly, the nonchiral N_{LP} phase can stay stable even in the presence of intrinsic chirality. PMID:27176241

  13. Sterically allowed configuration space for amino acid dipeptides

    NASA Astrophysics Data System (ADS)

    Caballero, Diego; Maatta, Jukka; Sammalkorpi, Maria; O'Hern, Corey; Regan, Lynne

    2014-03-01

    Despite recent improvements in computational methods for protein design, we still lack a quantitative, predictive understanding of the intrinsic propensities for amino acids to be in particular backbone or side-chain conformations. This question has remained unsettled for years because of the discrepancies between different experimental approaches. To address it, I performed all-atom hard-sphere simulations of hydrophobic residues with stereo-chemical constraints and non-attractive steric interactions between non-bonded atoms for ALA, ILE, LEU and VAL dipeptide mimetics. For these hard-sphere MD simulations, I show that transitions between α-helix and β-sheet structures only occur when the bond angle τ(N -Cα - C) >110° , and the probability distribution of bond angles for structures in the `bridge' region of ϕ- ψ space is shifted to larger angles compared to that in other regions. In contrast, the relevant bond-angle distributions obtained from most molecular dynamics packages are broader and shifter to larger values. I encounter similar correlations between bond angles and side-chain dihedral angles. The success of these studies is an argument for re-incorporating local stereochemical constraints into computational protein design methodology.

  14. Nano-Drugs Based on Nano Sterically Stabilized Liposomes for the Treatment of Inflammatory Neurodegenerative Diseases

    PubMed Central

    Turjeman, Keren; Bavli, Yaelle; Kizelsztein, Pablo; Schilt, Yaelle; Allon, Nahum; Katzir, Tamar Blumenfeld; Sasson, Efrat; Raviv, Uri; Ovadia, Haim; Barenholz, Yechezkel

    2015-01-01

    The present study shows the advantages of liposome-based nano-drugs as a novel strategy of delivering active pharmaceutical ingredients for treatment of neurodegenerative diseases that involve neuroinflammation. We used the most common animal model for multiple sclerosis (MS), mice experimental autoimmune encephalomyelitis (EAE). The main challenges to overcome are the drugs’ unfavorable pharmacokinetics and biodistribution, which result in inadequate therapeutic efficacy and in drug toxicity (due to high and repeated dosage). We designed two different liposomal nano-drugs, i.e., nano sterically stabilized liposomes (NSSL), remote loaded with: (a) a “water-soluble” amphipathic weak acid glucocorticosteroid prodrug, methylprednisolone hemisuccinate (MPS) or (b) the amphipathic weak base nitroxide, Tempamine (TMN). For the NSSL-MPS we also compared the effect of passive targeting alone and of active targeting based on short peptide fragments of ApoE or of β-amyloid. Our results clearly show that for NSSL-MPS, active targeting is not superior to passive targeting. For the NSSL-MPS and the NSSL-TMN it was demonstrated that these nano-drugs ameliorate the clinical signs and the pathology of EAE. We have further investigated the MPS nano-drug’s therapeutic efficacy and its mechanism of action in both the acute and the adoptive transfer EAE models, as well as optimizing the perfomance of the TMN nano-drug. The highly efficacious anti-inflammatory therapeutic feature of these two nano-drugs meets the criteria of disease-modifying drugs and supports further development and evaluation of these nano-drugs as potential therapeutic agents for diseases with an inflammatory component. PMID:26147975

  15. Nano-Drugs Based on Nano Sterically Stabilized Liposomes for the Treatment of Inflammatory Neurodegenerative Diseases.

    PubMed

    Turjeman, Keren; Bavli, Yaelle; Kizelsztein, Pablo; Schilt, Yaelle; Allon, Nahum; Katzir, Tamar Blumenfeld; Sasson, Efrat; Raviv, Uri; Ovadia, Haim; Barenholz, Yechezkel

    2015-01-01

    The present study shows the advantages of liposome-based nano-drugs as a novel strategy of delivering active pharmaceutical ingredients for treatment of neurodegenerative diseases that involve neuroinflammation. We used the most common animal model for multiple sclerosis (MS), mice experimental autoimmune encephalomyelitis (EAE). The main challenges to overcome are the drugs' unfavorable pharmacokinetics and biodistribution, which result in inadequate therapeutic efficacy and in drug toxicity (due to high and repeated dosage). We designed two different liposomal nano-drugs, i.e., nano sterically stabilized liposomes (NSSL), remote loaded with: (a) a "water-soluble" amphipathic weak acid glucocorticosteroid prodrug, methylprednisolone hemisuccinate (MPS) or (b) the amphipathic weak base nitroxide, Tempamine (TMN). For the NSSL-MPS we also compared the effect of passive targeting alone and of active targeting based on short peptide fragments of ApoE or of β-amyloid. Our results clearly show that for NSSL-MPS, active targeting is not superior to passive targeting. For the NSSL-MPS and the NSSL-TMN it was demonstrated that these nano-drugs ameliorate the clinical signs and the pathology of EAE. We have further investigated the MPS nano-drug's therapeutic efficacy and its mechanism of action in both the acute and the adoptive transfer EAE models, as well as optimizing the perfomance of the TMN nano-drug. The highly efficacious anti-inflammatory therapeutic feature of these two nano-drugs meets the criteria of disease-modifying drugs and supports further development and evaluation of these nano-drugs as potential therapeutic agents for diseases with an inflammatory component.

  16. Perspective: Vibrational-induced steric effects in bimolecular reactions

    SciTech Connect

    Liu, Kopin

    2015-02-28

    The concept of preferred collision geometry in a bimolecular reaction is at the heart of reaction dynamics. Exemplified by a series of crossed molecular beam studies on the reactions of a C–H stretch-excited CHD{sub 3}(v{sub 1} = 1) with F, Cl, and O({sup 3}P) atoms, two types of steric control of chemical reactivity will be highlighted. A passive control is governed in a reaction with strong anisotropic entry valley that can significantly steer the incoming trajectories. This disorientation effect is illustrated by the F and O({sup 3}P) + CHD{sub 3}(v{sub 1} = 1) reactions. In the former case, the long-range anisotropic interaction acts like an optical “negative” lens by deflecting the trajectories away from the favored transition-state geometry, and thus inhibiting the bond rupture of the stretch-excited CHD{sub 3}. On the contrary, the interaction between O({sup 3}P) and CHD{sub 3}(v{sub 1} = 1) behaves as a “positive” lens by funneling the large impact-parameter collisions into the cone of acceptance, and thereby enhances the reactivity. As for reactions with relatively weak anisotropic interactions in the entry valley, an active control can be performed by exploiting the polarization property of the infrared excitation laser to polarize the reactants in space, as demonstrated in the reaction of Cl with a pre-aligned CHD{sub 3}(v{sub 1} = 1) reactant. A simpler case, the end-on versus side-on collisions, will be elucidated for demonstrating a means to disentangle the impact-parameter averaging. A few general remarks about some closely related issues, such as mode-, bond-selectivity, and Polanyi’s rules, are made.

  17. Comprehensive Examination of Barriers to Employment among Persons Who Are Blind or Visually Impaired.

    ERIC Educational Resources Information Center

    Crudden, Adele; McBroom, Lynn W.; Skinner, Amy L.; Moore, J. Elton

    A survey of 166 employed persons with visual impairments investigated major barriers to employment, how these barriers were overcome, and their perceptions on why they were successful in overcoming barriers when many individuals are not successful. Results of the survey indicate that the primary barriers to employment were employer attitudes,…

  18. Photocleavage control of nucleated DNA nanosystems--the influence of surface strand sterics.

    PubMed

    Hanna, Morcos; Munshi, Moorsalin; Kedzierski, Nancy A; Chung, Paul N; Huang, Terry; Mok, Allen K; Lukeman, Philip S

    2014-02-21

    We use sterically inaccessible 'seed' strands, released from a surface into solution by photocleavage to initiate a nucleated DNA polymerization reaction. We demonstrate control of the quantity of 'seed' release and that hairpin steric protection of the 'seed' leads to less 'leaky' surfaces. This polymerization is a model system for surface-photocleavage initiation of sub-stoichiometric reaction cascades; these cascades should find use as a component of labs-on-chips capable of bioanalytical and DNA-computing tasks. PMID:24402244

  19. Photocleavage control of nucleated DNA nanosystems--the influence of surface strand sterics.

    PubMed

    Hanna, Morcos; Munshi, Moorsalin; Kedzierski, Nancy A; Chung, Paul N; Huang, Terry; Mok, Allen K; Lukeman, Philip S

    2014-02-21

    We use sterically inaccessible 'seed' strands, released from a surface into solution by photocleavage to initiate a nucleated DNA polymerization reaction. We demonstrate control of the quantity of 'seed' release and that hairpin steric protection of the 'seed' leads to less 'leaky' surfaces. This polymerization is a model system for surface-photocleavage initiation of sub-stoichiometric reaction cascades; these cascades should find use as a component of labs-on-chips capable of bioanalytical and DNA-computing tasks.

  20. In Vivo Gene Delivery by Nonviral Vectors: Overcoming Hurdles?

    PubMed Central

    Zhang, Yuan; Satterlee, Andrew; Huang, Leaf

    2012-01-01

    The promise of cancer gene therapeutics is hampered by difficulties in the in vivo delivery to the targeted tumor cells, and systemic delivery remains to be the biggest challenge to be overcome. Here, we concentrate on systemic in vivo gene delivery for cancer therapy using nonviral vectors. In this review, we summarize the existing delivery barriers together with the requirements and strategies to overcome these problems. We will also introduce the current progress in the design of nonviral vectors, and briefly discuss their safety issues. PMID:22525514

  1. Helping Young Children Overcome Shyness.

    ERIC Educational Resources Information Center

    Malouff, John

    This paper examines shyness--its causes and its impact on children--and presents several strategies based on social learning theory for parents and teachers to help young children overcome shyness. The paper also describes a personal application of these strategies on a young girl. The strategies presented for parents and teachers are: (1) tell…

  2. Diffusion barriers

    NASA Technical Reports Server (NTRS)

    Nicolet, M. A.

    1983-01-01

    The choice of the metallic film for the contact to a semiconductor device is discussed. One way to try to stabilize a contact is by interposing a thin film of a material that has low diffusivity for the atoms in question. This thin film application is known as a diffusion barrier. Three types of barriers can be distinguished. The stuffed barrier derives its low atomic diffusivity to impurities that concentrate along the extended defects of a polycrystalline layer. Sacrificial barriers exploit the fact that some (elemental) thin films react in a laterally uniform and reproducible fashion. Sacrificial barriers have the advantage that the point of their failure is predictable. Passive barriers are those most closely approximating an ideal barrier. The most-studied case is that of sputtered TiN films. Stuffed barriers may be viewed as passive barriers whose low diffusivity material extends along the defects of the polycrystalline host.

  3. Overcoming Stereotypes, Discovering Hidden Capitals

    ERIC Educational Resources Information Center

    Beckett, Lori; Wrigley, Terry

    2014-01-01

    This article presents a model of teacher research supported by academic partners to develop a better understanding of the barriers to education faced by young people growing up in poverty. It critiques politicians' demands for teachers to "close the gap" for ignoring the cumulative intergenerational effects of deprivation. The…

  4. Measuring Transmembrane Helix Interaction Strengths in Lipid Bilayers Using Steric Trapping

    PubMed Central

    Hong, Heedeok; Chang, Yu-Chu; Bowie, James U.

    2016-01-01

    We have developed a method to measure strong transmembrane (TM) helix interaction affinities in lipid bilayers that are difficult to measure by traditional dilution methods. The method, called steric trapping, couples dissociation of biotinylated TM helices to a competitive binding by monovalent streptavidin (mSA), so that dissociation is driven by the affinity of mSA for biotin and mSA concentration. By adjusting the binding affinity of mSA through mutation, the method can obtain dissociation constants of TM helix dimers (Kd,dimer) over a range of six orders of magnitudes. The Kd,dimer limit of measurable target interaction is extended 3–4 orders of magnitude lower than possible by dilution methods. Thus, steric trapping opens up new opportunities to study the folding and assembly of α-helical membrane proteins in lipid bilayer environments. Here we provide detailed methods for applying steric trapping to a TM helix dimer. PMID:23975771

  5. The predicted role of steric specificity in crowding-mediated effects on reversible biomolecular association

    NASA Astrophysics Data System (ADS)

    Powers, J. D.; Castle, B. T.; Odde, D. J.

    2015-12-01

    A fundamental question in biology is whether the presence of non-reacting macromolecules in the cytoplasm affects the rates and extents of reversible association reactions, a phenomenon often referred to as ‘macromolecular crowding.’ Under certain conditions, crowding has been proposed to dramatically alter the kinetics and thermodynamics of chemical reactions, making it difficult to quantitatively relate rates and extents of reactions measured in vitro to those occurring in vivo. In this work, we use Brownian dynamics simulation and Monte Carlo methods to (1) quantify the overall thermodynamic and kinetic effects of crowding by independently investigating each step of reversible bimolecular association (i.e. translational diffusion, steric specific binding, and dissociation), and (2) provide an explicit, quantitative investigation of how the degree of steric specificity of protein dimerization influences crowding-mediated effects on association and dissociation. We find that k on decreases by ˜2-fold for non-steric specific reactions, and increases by ˜3-fold for highly steric specific reactions. In addition, k off decreases by only ˜30%-60% in the presence of crowders, depending on the strength of the bond between the reactant pair, so that the equilibrium constant is increased by ˜4-fold, at most. These results suggest that crowding-mediated effects on globular protein dimerization reactions in the cytoplasm are modulated by the steric specificity of the reactants, and that reversible protein-protein association is relatively insensitive to the physical presence of crowders (i.e. steric repulsion effects in the cytoplasm) for crowders of similar size and shape to reactants over a range of volume fractions (0-0.3).

  6. Epistemological barriers to radical behaviorism

    PubMed Central

    O'Donohue, William T.; Callaghan, Glenn M.; Ruckstuhl, L. E.

    1998-01-01

    The historian and philosopher of science Gaston Bachelard proposed the concept of epistemological barriers to describe the intellectual challenges encountered by scientists in their work. In order to embrace novel ways of approaching a problem in science, scientists must overcome barriers or obstacles posed by their prior views. For example, Einsteinian physics presents scientists with claims that space is curved and that time and space are on the same continuum. We utilize Bachelard's concept of epistemological barriers to describe the differences between the intellectual journeys students pursuing advanced studies face when attempting to accept cognitive psychology or radical behaviorism. We contend that the folk psychological beliefs that students typically hold when entering these studies pose less challenge to cognitive psychology than to radical behaviorism. We also suggest that these barriers may also partly be involved in the problematic exegesis that has plagued radical behaviorism. In close, we offer some suggestions for dealing with these epistemological barriers. PMID:22478314

  7. Strategies to overcome statin intolerance.

    PubMed

    Agouridis, Aris P; Nair, Devaki R; Mikhailidis, Dimitri P

    2015-06-01

    This editorial discusses several options to overcome statin intolerance in clinical practice. For example, switching to a different statin, changing statin dosing, using lipid-lowering drugs other than statins (e.g., ezetimibe, bile acid sequestrants and fibrates, alone or in combination), or combining statins with other lipid-lowering drugs. The authors focus on the potential mechanisms involved in statin-related myopathy. New lipid-lowering drugs currently in development (e.g., cholesterol ester transfer protein inhibitors [anacetrapib] and proprotein convertase subtilisin/kexin 9 inhibitors) inhibitors may help in the management of statin intolerance while achieving low-density lipoprotein cholesterol targets as set out by the guidelines.

  8. Barriers to Physical Activity Among Gay Men.

    PubMed

    Cary, Miranda A; Brittain, Danielle R; Dinger, Mary K; Ford, Melissa L; Cain, Meagan; Sharp, Teresa A

    2016-09-01

    Gay men may not be physically active at recommended levels to achieve health benefits. Thus, a need exists to identify general (i.e., common across populations) and population-specific barriers that hinder or stop gay men from participating in physical activity (PA). Salient barriers may be identified through the extent each barrier limits PA (i.e., barrier limitation) and the level of one's confidence to overcome barriers and engage in PA (i.e., self-regulatory efficacy). The purposes of this study were to (1) provide a description of general and population-specific barriers to PA among sufficiently and insufficiently active gay men, (2) identify barrier limitation and self-regulatory efficacy for the reported barriers, and (3) examine the associations between meeting the current PA recommendation, barrier limitation, and self-regulatory efficacy. Participants were 108 self-identified gay males aged 21 to 64 years who completed a web-based survey. A total of 35 general barriers and no population-specific barriers were identified by the sufficiently and insufficiently active groups. The sufficiently active group reported higher self-regulatory efficacy and lower barrier limitation for nearly all reported barriers. A binary logistic regression used to examine the associations between PA, barrier limitation, and self-regulatory efficacy was statistically significant, χ(2)(2, N = 108) = 19.26, p < .0001, R(2) = .16. Only barrier limitation significantly contributed to the model. Future research should continue to examine barriers to PA among gay men to determine whether an intervention needs to be designed specifically for gay men or whether a one-size-fits-all intervention would be effective in helping all men overcome common barriers to engaging in PA.

  9. Overcoming Barriers to Leadership by Women--Identification of Barriers: A Psycho-Social Perspective.

    ERIC Educational Resources Information Center

    Hoferek, Mary J.

    Recent data indicate that women are underutilized and underrepresented in leadership roles in physical education at the higher education level, that the degree of underutilization and underrepresentation increases with the degree of power associated with the role in question, and that this situation is typical also of higher education in general…

  10. Implications of sterically constrained n-butane oxidation reactions on the reaction mechanism and selectivity to 1-butanol

    NASA Astrophysics Data System (ADS)

    Dix, Sean T.; Gómez-Gualdrón, Diego A.; Getman, Rachel B.

    2016-11-01

    Density functional theory (DFT) is used to analyze the reaction network in n-butane oxidation to 1-butanol over a Ag/Pd alloy catalyst under steric constraints, and the implications on the ability to produce 1-butanol selectively using MOF-encapsulated catalysts are discussed. MOFs are porous crystalline solids comprised of metal nodes linked by organic molecules. Recently, they have been successfully grown around metal nanoparticle catalysts. The resulting porous networks have been shown to promote regioselective chemistry, i.e., hydrogenation of trans-1,3-hexadiene to 3-hexene, presumably by forcing the linear alkene to stand "upright" on the catalyst surface and allowing only the terminal C-H bonds to be activated. In this work, we extend this concept to alkane oxidation. Our goal is to determine if a MOF-encapsulated catalyst could be used to selectively produce 1-butanol. Reaction energies and activation barriers are presented for more than 40 reactions in the pathway for n-butane oxidation. We find that C-H bond activation proceeds through an oxygen-assisted pathway and that butanal and 1-butanol are some of the possible products.

  11. New sterically stabilized vesicles based on nonionic surfactant, cholesterol, and poly(ethylene glycol)-cholesterol conjugates.

    PubMed Central

    Beugin, S; Edwards, K; Karlsson, G; Ollivon, M; Lesieur, S

    1998-01-01

    Monomethoxypoly(ethylene glycol) cholesteryl carbonates (M-PEG-Chol) with polymer chain molecular weights of 1000 (M-PEG1000-Chol) and 2000 (M-PEG2000-Chol) have been newly synthesized and characterized. Their aggregation behavior in mixture with diglycerol hexadecyl ether (C16G2) and cholesterol has been examined by cryotransmission electron microscopy, high-performance gel exclusion chromatography, and quasielastic light scattering. Nonaggregated, stable, unilamellar vesicles were obtained at low polymer levels with optimal shape and size homogeneity at cholesteryl conjugate/ lipids ratios of 10 mol% M-PEG1000-Chol or 5 mol% M-PEG2000-Chol, corresponding to the theoretically predicted brush conformational state of the PEG chains. At 20 mol% M-PEG1000-Chol or 10 mol% M-PEG2000-Chol, the saturation threshold of the C16G2/cholesterol membrane in polymer is exceeded, and open disk-shaped aggregates are seen in coexistence with closed vesicles. Higher levels up to 30 mol% lead to the complete solubilization of the vesicles into disk-like structures of decreasing size with increasing PEG content. This study underlines the bivalent role of M-PEG-Chol derivatives: while behaving as solubilizing surfactants, they provide an efficient steric barrier, preventing the vesicles from aggregation and fusion over a period of at least 2 weeks. PMID:9635773

  12. OXIDATION OF CYCLOHEXANE WITH AIR CATALYZED BY A STERICALLY HINDERED IRON (II) COMPLEX

    EPA Science Inventory

    Oxidation of Cyclohexane with Air Catalyzed by a Sterically Hindered Iron(II) Complex.


    Thomas M. Becker, Michael A. Gonzalez*

    United States Environmental Protection Agency; National Risk Management Research Laboratory; Sustainable Technology Division; Clean Pr...

  13. Steric stabilization of nonaqueous silicon slips. I - Control of particle agglomeration and packing. II - Pressure casting of powder compacts

    NASA Technical Reports Server (NTRS)

    Kerkar, Awdhoot V.; Henderson, Robert J. M.; Feke, Donald L.

    1990-01-01

    The application of steric stabilization to control particle agglomeration and packing of silicon powder in benzene and trichloroethylene is reported. The results provide useful guidelines for controlling unfavorable particle-particle interactions during nonaqueous processing of silicon-based ceramic materials. The application of steric stabilization to the control and improvement of green processing of nonaqueous silicon slips in pressure consolidation is also demonstrated.

  14. Barriers to Asthma Management as Identified by School Nurses

    ERIC Educational Resources Information Center

    Quaranta, Judith E.; Spencer, Gale A.

    2016-01-01

    Asthma rates are increasing in children. School nurses have opportunities to care for children with asthma but need to overcome barriers impacting their ability to manage asthma in the school setting. This study (a) assessed barriers present in the school setting, (b) determined the impact of barriers on performance of asthma management behaviors,…

  15. Vehicle barrier

    DOEpatents

    Hirsh, Robert A.

    1991-01-01

    A vehicle security barrier which can be conveniently placed across a gate opening as well as readily removed from the gate opening to allow for easy passage. The security barrier includes a barrier gate in the form of a cable/gate member in combination with laterally attached pipe sections fixed by way of the cable to the gate member and lateral, security fixed vertical pipe posts. The security barrier of the present invention provides for the use of cable restraints across gate openings to provide necessary security while at the same time allowing for quick opening and closing of the gate areas without compromising security.

  16. Overcoming challenges in improvement work.

    PubMed

    Crisp, Helen

    2013-09-01

    The Health Foundation is an independent charity working to improve healthcare in the UK, so that we have a system of the highest possible quality-safe, effective, person-centred, timely, efficient and equitable. We believe that in order to achieve this, health services need to continually improve the way they work. The Foundation conducts research and evaluation, puts ideas into practice through improvement programmes, develops leaders and shares evidence to drive wider change. The work is a focused around two priority areas: patient safety and person-centred care. The Foundation has supported work to improve services for patients with kidney disease and, in common with other quality improvement projects, there have been challenges to overcome. Awareness of these common challenges can help others to be more prepared when planning service improvements.

  17. Overcoming "the Valley of Death".

    PubMed

    McIntyre, Robin A

    2014-01-01

    On a global level there are major challenges arising from climate change, resource use and changing age demographics. These issues have created a global marketplace for novel innovative products and solutions which can help to combat and overcome these challenges which have created significant commercial opportunities for companies, particularly for small and medium size enterprises or SMEs. Companies most likely to take advantage of these opportunities will be those which can innovate in a timely manner. Innovation significantly contributes to higher productivity and economic growth, and is core to a company's competitiveness within often challenging marketplaces. However, many factors can stifle innovation. Companies can struggle to identify finance for early-stage development, the returns can be difficult to predict, and the innovation 'landscape' is often complex and unclear. This brief review describes some of the main issues with commercialising innovative ideas and provides guidance with respect to the often complicated funding landscape both on a National and European level.

  18. Overcoming "the Valley of Death".

    PubMed

    McIntyre, Robin A

    2014-01-01

    On a global level there are major challenges arising from climate change, resource use and changing age demographics. These issues have created a global marketplace for novel innovative products and solutions which can help to combat and overcome these challenges which have created significant commercial opportunities for companies, particularly for small and medium size enterprises or SMEs. Companies most likely to take advantage of these opportunities will be those which can innovate in a timely manner. Innovation significantly contributes to higher productivity and economic growth, and is core to a company's competitiveness within often challenging marketplaces. However, many factors can stifle innovation. Companies can struggle to identify finance for early-stage development, the returns can be difficult to predict, and the innovation 'landscape' is often complex and unclear. This brief review describes some of the main issues with commercialising innovative ideas and provides guidance with respect to the often complicated funding landscape both on a National and European level. PMID:25549408

  19. Microbial barriers.

    PubMed

    Gutwein, Luke G; Panigrahi, Mousumee; Schultz, Gregory S; Mast, Bruce A

    2012-07-01

    Barrier wound therapy is commonplace in the health care environment and functions to limit bacterial colonization and infection in both acute wounds and recalcitrant chronic wounds. This article reviews the nature of acute and chronic wounds and their available adjunctive barrier therapies.

  20. Adsorption of sterically stabilized latex particles at liquid surfaces: effects of steric stabilizer surface coverage, particle size, and chain length on particle wettability.

    PubMed

    Reed, K M; Borovicka, J; Horozov, T S; Paunov, V N; Thompson, K L; Walsh, A; Armes, S P

    2012-05-01

    A series of five near-monodisperse sterically stabilized polystyrene (PS) latexes were synthesized using three well-defined poly(glycerol monomethacrylate) (PGMA) macromonomers with mean degrees of polymerization (DP) of 30, 50, or 70. The surface coverage and grafting density of the PGMA chains on the particle surface were determined using XPS and (1)H NMR spectroscopy, respectively. The wettability of individual latex particles adsorbed at the air-water and n-dodecane-water interfaces was studied using both the gel trapping technique and the film calliper method. The particle equilibrium contact angle at both interfaces is relatively insensitive to the mean DP of the PGMA stabilizer chains. For a fixed stabilizer DP of 30, particle contact angles were only weakly dependent on the particle size. The results are consistent with a model of compact hydrated layers of PGMA stabilizer chains at the particle surface over a wide range of grafting densities. Our approach could be utilized for studying the adsorption behavior of a broader range of sterically stabilized inorganic and polymeric particles of practical importance. PMID:22502638

  1. Structural peculiarities of configurational isomers of 1-styrylpyrroles according to 1Н, 13С and 15N NMR spectroscopy and density functional theory calculations: electronic and steric hindrance for planar structure.

    PubMed

    Afonin, Andrei V; Ushakov, Igor A; Pavlov, Dmitry V; Schmidt, Elena Yu; Dvorko, Marina Yu

    2013-06-01

    Comparative analysis of the (1)Н and (13)С NMR data for a series of the E and Z-1-styrylpyrroles, E and Z-1-(1-propenyl)pyrroles, 1-vinylpyrroles and styrene suggests that the conjugation between the unsaturated fragments in the former compounds is reduced. This is the result of the mutual influence of the donor p-π and π-π conjugation having opposite directions. According to the NMR data combined with the density functional theory calculations, the Z isomer of 1-styrylpyrrole has essentially a nonplanar structure because of the steric hindrance. However, the E isomer of 1-styrylpyrrole is also an out-of-plane structure despite the absence of a sterical barrier for the planar one. Deviation of the E isomer from the planar structure seems to be caused by an electronic hindrance produced by a mutual influence of the p-π and π-π conjugation. The structure of the E isomer of the 2-substituted 1-styrylpyrroles is similar to that of the 2-substituted 1-vinylpyrroles. The steric effects in the Z isomer of the 2-substituted 1-styrylpyrroles result in the large increase of the dihedral angle between planes of the pyrrole ring and double bond. PMID:23558848

  2. Synthesis and characterisation of an N-heterocyclic carbene with spatially-defined steric impact.

    PubMed

    Shaw, Paul; Kennedy, Alan R; Nelson, David J

    2016-08-01

    The synthesis and co-ordination chemistry of a new 'bulky yet flexible' N-heterocyclic carbene ("IPaul") is reported. This carbene has spatially-defined steric impact; steric maps show that two quadrants are very bulky while the other two are quite open. The electronic properties of this carbene are very similar to those of other 1,3-diarylimidazol-2-ylidenes. Copper, silver, iridium, and nickel complexes of the new ligand have been prepared. In solution, the ligand adopts two different conformations, while X-ray crystallographic analyses of the transition metal complexes suggest that the syn-conformer is preferred in the solid state due to intermolecular interactions. The copper(i) chloride complex of this new ligand has been shown to be highly-active in the hydrosilylation of carbonyl compounds, when compared to the analogous IPr, IMes, IPr* and IPr*(OMe) complexes. PMID:27335266

  3. Tuning steric and electronic effects in transition-metal β-diketiminate complexes

    PubMed Central

    Chen, Chi; Bellows, Sarina M.; Holland, Patrick L.

    2015-01-01

    β-Diketiminates are widely used supporting ligands for building a range of metal complexes with different oxidation states, structures, and reactivities. This Perspective summarizes the steric and electronic influences of ligand substituents on these complexes, with an eye toward informing the design of new complexes with optimized properties. The backbone and N-aryl substituents can give significant steric effects on structure, reactivity and selectivity of reactions. The electron density on the metal can be tuned by installation of electron withdrawing or donating groups on the β-diketiminate ligand as well. Examples are shown from throughout the transition metal series to demonstrate different types of effects attributable to systematic variation of β-diketiminate ligands. PMID:26244489

  4. The Role of Aryne Distortions, Steric Effects, and Charges in Regioselectivities of Aryne Reactions

    PubMed Central

    2015-01-01

    The distortion/interaction model has been used to explain and predict reactivity in a variety of reactions where more common explanations, such as steric and electronic factors, do not suffice. This model has also provided new fundamental insight into regioselectivity trends in reactions of unsymmetrical arynes, which in turn has fueled advances in aryne methodology and natural product synthesis. This article describes a systematic experimental and computational study of one particularly important class of arynes, 3-halobenzynes. 3-Halobenzynes are useful synthetic building blocks whose regioselectivities have been explained by several different models over the past few decades. Our efforts show that aryne distortion, rather than steric factors or charge distribution, are responsible for the regioselectivities observed in 3-haloaryne trapping experiments. We also demonstrate the synthetic utility of 3-halobenzynes for the efficient synthesis of functionalized heterocycles, using a tandem aryne-trapping/cross-coupling sequence involving 3-chlorobenzyne. PMID:25303232

  5. Electrocatalytic Alcohol Oxidation with TEMPO and Bicyclic Nitroxyl Derivatives: Driving Force Trumps Steric Effects.

    PubMed

    Rafiee, Mohammad; Miles, Kelsey C; Stahl, Shannon S

    2015-11-25

    Bicyclic nitroxyl derivatives, such as 2-azaadamantane N-oxyl (AZADO) and 9-azabicyclo[3.3.1]nonane N-oxyl (ABNO), have emerged as highly effective alternatives to TEMPO-based catalysts for selective oxidation reactions (TEMPO = 2,2,6,6-tetramethyl-1-piperidine N-oxyl). Their efficacy is widely attributed to their smaller steric profile; however, electrocatalysis studies described herein show that the catalytic activity of nitroxyls is more strongly affected by the nitroxyl/oxoammonium redox potential than by steric effects. The inexpensive, high-potential TEMPO derivative, 4-acetamido-TEMPO (ACT), exhibits higher electrocatalytic activity than AZADO and ABNO for the oxidation of primary and secondary alcohols. Mechanistic studies provide insights into the origin of these unexpected reactivity trends. The superior activity of ACT is especially noteworthy at high pH, where bicyclic nitroxyls are inhibited by formation of an oxoammonium hydroxide adduct.

  6. Using steric hindrance to design new inhibitors of class C beta-lactamases

    SciTech Connect

    Trehan, Indi; Morandi, F.; Blaszczak, L.C.; Shoichet, Brian K.

    2010-03-08

    {beta}-lactamases confer resistance to {beta}-lactam antibiotics such as penicillins and cephalosporins. However, {beta}-lactams that form an acyl-intermediate with the enzyme but subsequently are hindered from forming a catalytically competent conformation seem to be inhibitors of {beta}-lactamases. This inhibition may be imparted by specific groups on the ubiquitous R1 side chain of {beta}-lactams, such as the 2-amino-4-thiazolyl methoxyimino (ATMO) group common among third-generation cephalosporins. Using steric hindrance of deacylation as a design guide, penicillin and carbacephem substrates were converted into effective {beta}-lactamase inhibitors and antiresistance antibiotics. To investigate the structural bases of inhibition, the crystal structures of the acyl-adducts of the penicillin substrate amoxicillin and the new analogous inhibitor ATMO-penicillin were determined. ATMO-penicillin binds in a catalytically incompetent conformation resembling that adopted by third-generation cephalosporins, demonstrating the transferability of such sterically hindered groups in inhibitor design.

  7. Abstraction of iodine from aromatic iodides by alkyl radicals: steric and electronic effects.

    PubMed

    Dolenc, Darko; Plesnicar, Bozo

    2006-10-13

    Abstraction of the iodine atom from aryl iodides by alkyl radicals takes place in some cases very efficiently despite the unfavorable difference in bond dissociation energies of C-I bonds in alkyl and aryl iodides. The abstraction is most efficient in iodobenzenes, ortho-substituted with bulky groups. The ease of abstraction can be explained by the release of steric strain during the elimination of the iodine atom. The rate of abstraction correlates fairly well with the strain energy, calculated by density functional theory (DFT) and Hartree-Fock (HF) methods as a difference in the total energy of ortho and para isomers. However, besides the steric bulk, the presence of some other functional groups in an ortho substituent also influences the rate. The stabilization of the transition state, resembling a 9-I-2 iodanyl radical, by electron-withdrawing groups seems to explain a positive sign of the Hammett rho value in the radical abstraction of halogen atoms. PMID:17025291

  8. Steric clashes determine differences in side chain dihedral angle distributions: A study of Thr versus Val

    NASA Astrophysics Data System (ADS)

    Zhou, Alice; O'Hern, Corey; Regan, Lynne

    2012-02-01

    With the long-term goal to improve the design of protein-protein interactions, we develop a simple hard sphere model for dipeptides that can predict the side-chain dihedral angle distributions of Val and Thr in both the α-helix and β-sheet backbone conformations. We find that it is essential to include the non-polar hydrogens in the model; indeed interatomic clashes involving the non-polar hydrogens largely determine the form of side-chain dihedral angle distributions. Further, we are able to explain key differences in the side-chain dihedral angle distributions for Val and Thr from intra-residue steric clashes rather than inter-residue steric clashes or hydrogen bonding. These results are the crucial first step in developing computational models that can predict the side chain conformations of residues at protein-peptide interfaces.

  9. Chromatography Models with Langmuir and Steric Mass Action Adsorption Isotherms are of Differential Index One

    NASA Astrophysics Data System (ADS)

    von Lieres, Eric

    2010-09-01

    Chromatography is commonly applied for the separation of bio-molecules in pharmaceutical industry, and chromatography models are increasingly applied for rational process analysis and optimization. A rapid equilibrium assumption is often applied for the adsorption equation, which results in a non-linear system of partial differential-algebraic equations (PDAEs). In this contribution a proof is given, that these PDAEs are of differential index one for the two most prominent isotherm models, Langmuir and steric mass action (SMA).

  10. Relationship between vesicle size and steric hindrance influences vesicle rupture on solid supports.

    PubMed

    Jackman, Joshua A; Kim, Min Chul; Zhdanov, Vladimir P; Cho, Nam-Joon

    2016-01-28

    Phospholipid assemblies on solid supports mimic the cell membrane, and provide a platform to study membrane biology. Among the different types of model membranes, the planar bilayer is a two-dimensional lipid bilayer sheet that can be formed by the adsorption and spontaneous rupture of vesicles. The formation process is influenced by the interactions between vesicles and the solid support as well as between vesicles. On silicon oxide, which is a commonly used solid support, vesicles typically adsorb until reaching a critical coverage and then spontaneous rupture begins. Although it is generally understood that spontaneous rupture leads to planar bilayer formation, oversaturation of vesicles at the critical coverage can hinder the whole process due to a steric factor. To date, the role of this factor has been scrutinized only in relation to temperature, and the influence of additional parameters remains to be elucidated. In this work, we have investigated how vesicle size and corresponding steric constraints influence the kinetics of vesicle adsorption and rupture and, more specifically, how the state of adsorbed vesicles after fusion depends on the vesicle size. Using quartz crystal microbalance-dissipation (QCM-D) and fluorescence recovery after photobleaching (FRAP), we characterized the adsorption kinetics of vesicles onto silicon oxide and the lateral mobility of solid-supported lipid assemblies. While the vesicle adsorption kinetics were diffusion-limited up to the onset of vesicle rupture, the extent of rupture depended on vesicle size and it was observed that larger vesicles are more prone to steric effects than smaller vesicles. We discuss this finding in terms of the structural transformation from adsorbed vesicles to a planar bilayer, including how the interplay of thermodynamic, kinetic and steric factors can affect vesicle rupture on solid supports. PMID:26739602

  11. Relationship between vesicle size and steric hindrance influences vesicle rupture on solid supports.

    PubMed

    Jackman, Joshua A; Kim, Min Chul; Zhdanov, Vladimir P; Cho, Nam-Joon

    2016-01-28

    Phospholipid assemblies on solid supports mimic the cell membrane, and provide a platform to study membrane biology. Among the different types of model membranes, the planar bilayer is a two-dimensional lipid bilayer sheet that can be formed by the adsorption and spontaneous rupture of vesicles. The formation process is influenced by the interactions between vesicles and the solid support as well as between vesicles. On silicon oxide, which is a commonly used solid support, vesicles typically adsorb until reaching a critical coverage and then spontaneous rupture begins. Although it is generally understood that spontaneous rupture leads to planar bilayer formation, oversaturation of vesicles at the critical coverage can hinder the whole process due to a steric factor. To date, the role of this factor has been scrutinized only in relation to temperature, and the influence of additional parameters remains to be elucidated. In this work, we have investigated how vesicle size and corresponding steric constraints influence the kinetics of vesicle adsorption and rupture and, more specifically, how the state of adsorbed vesicles after fusion depends on the vesicle size. Using quartz crystal microbalance-dissipation (QCM-D) and fluorescence recovery after photobleaching (FRAP), we characterized the adsorption kinetics of vesicles onto silicon oxide and the lateral mobility of solid-supported lipid assemblies. While the vesicle adsorption kinetics were diffusion-limited up to the onset of vesicle rupture, the extent of rupture depended on vesicle size and it was observed that larger vesicles are more prone to steric effects than smaller vesicles. We discuss this finding in terms of the structural transformation from adsorbed vesicles to a planar bilayer, including how the interplay of thermodynamic, kinetic and steric factors can affect vesicle rupture on solid supports.

  12. Palladium-catalyzed cross-coupling of sterically demanding boronic acids with α-bromocarbonyl compounds.

    PubMed

    Zimmermann, Bettina; Dzik, Wojciech I; Himmler, Thomas; Goossen, Lukas J

    2011-10-01

    A catalyst system generated in situ from Pd(dba)(2) and tri(o-tolyl)phosphine mediates the coupling of arylboronic acids with alkyl α-bromoacetates under formation of arylacetic acid esters at unprecedented low loadings. The new protocol, which involves potassium fluoride as the base and catalytic amounts of benzyltriethylammonium bromide as a phase transfer catalyst, is uniquely effective for the synthesis of sterically demanding arylacetic acid derivatives.

  13. 21st century Mediterranean sea level rise: Steric and atmospheric pressure contributions from a regional model

    NASA Astrophysics Data System (ADS)

    Tsimplis, Michael N.; Marcos, Marta; Somot, Samuel

    2008-09-01

    An Atmosphere-Ocean Regional Climate Model coupled over the Mediterranean basin and forced by river runoff and influxes from the Atlantic Ocean and the Black Sea is used to obtain estimates of sea level rise in the region during the 21st century. Changes in temperature and salinity under the A2 emission scenario, which corresponds to a high level of anthropogenic gas concentration in the atmosphere, are investigated in the different sub-basins and are used to compute the steric sea level change in the region. Significant spatial variability is observed. This model projects a maximum steric sea level rise of 25 cm. The mean steric sea level rise value predicted is around 13 cm with lower values in the eastern Mediterranean and higher values at the western Mediterranean. Coastal sea level rise values are found to be smaller, although this is partly due to the smaller range of vertical integration in the computation of sea level changes. Warming and salinification of the intermediate waters are also predicted to occur simultaneously thus partly compensating each other. The effects of atmospheric pressure changes are added to the steric sea level obtained from the model giving up to 2 mbars and thus also compensating some of the thermal expansion. Circulation changes will in certain areas also add up to 6 cm of sea level rise. There is no predicted seasonal bias in the sea level rise indicating that the seasonal cycles will remain unaffected. These results are derived from a single model and therefore can only been seen as part of a methodological study. Similar investigations should be applied to a range of models and scenarios in order to obtain a range of the future sea level change in the Mediterranean basin and its associated uncertainties.

  14. Steric Shielding of Surface Epitopes and Impaired Immune Recognition Induced by the Ebola Virus Glycoprotein

    PubMed Central

    Francica, Joseph R.; Varela-Rohena, Angel; Medvec, Andrew; Plesa, Gabriela; Riley, James L.; Bates, Paul

    2010-01-01

    Many viruses alter expression of proteins on the surface of infected cells including molecules important for immune recognition, such as the major histocompatibility complex (MHC) class I and II molecules. Virus-induced downregulation of surface proteins has been observed to occur by a variety of mechanisms including impaired transcription, blocks to synthesis, and increased turnover. Viral infection or transient expression of the Ebola virus (EBOV) glycoprotein (GP) was previously shown to result in loss of staining of various host cell surface proteins including MHC1 and β1 integrin; however, the mechanism responsible for this effect has not been delineated. In the present study we demonstrate that EBOV GP does not decrease surface levels of β1 integrin or MHC1, but rather impedes recognition by steric occlusion of these proteins on the cell surface. Furthermore, steric occlusion also occurs for epitopes on the EBOV glycoprotein itself. The occluded epitopes in host proteins and EBOV GP can be revealed by removal of the surface subunit of GP or by removal of surface N- and O- linked glycans, resulting in increased surface staining by flow cytometry. Importantly, expression of EBOV GP impairs CD8 T-cell recognition of MHC1 on antigen presenting cells. Glycan-mediated steric shielding of host cell surface proteins by EBOV GP represents a novel mechanism for a virus to affect host cell function, thereby escaping immune detection. PMID:20844579

  15. Does Size Really Matter? The Steric Isotope Effect in a Supramolecular Host?Guest Exchange Reaction

    SciTech Connect

    Mugridge, Jeffrey; Bergman, Robert; Raymond, Kenneth

    2010-01-29

    Isotope effects (IEs), which arise from differences in zero point energies (ZPEs) between a parent and isotopically substituted bond, have been used extensively by chemists to probe molecular interactions and reactivity. Due to the anharmonicity of the C-H/D vibrational potential energy function and the lower ZPE of a C-D bond, the average C-D bond length is typically {approx}0.005 {angstrom} shorter than an equivalent C-H bond. It is this difference in size that is often invoked to explain the observation of secondary, inverse kinetic isotope effects (KIEs) in chemical processes which proceed through a sterically strained transition state. This so-called 'steric isotope effect' (SIE) has been observed in processes such as the racemization of ortho-substituted biphenyls[6] and phenanthrenes, ring flipping of cyclophanes, and more recently in the deslipping of rotaxanes, where substitution of the sterically less demanding deuterium for protium results in rate accelerations for these processes. Herein, we use deuterium substitution in a cationic guest molecule to probe the sensitivity limits of the guest exchange process from a highly-charged supramolecular host.

  16. Glucocorticosteroids in nano-sterically stabilized liposomes are efficacious for elimination of the acute symptoms of experimental cerebral malaria.

    PubMed

    Waknine-Grinberg, Judith H; Even-Chen, Simcha; Avichzer, Jasmine; Turjeman, Keren; Bentura-Marciano, Annael; Haynes, Richard K; Weiss, Lola; Allon, Nahum; Ovadia, Haim; Golenser, Jacob; Barenholz, Yechezkel

    2013-01-01

    Cerebral malaria is the most severe complication of Plasmodium falciparum infection, and a leading cause of death in children under the age of five in malaria-endemic areas. We report high therapeutic efficacy of a novel formulation of liposome-encapsulated water-soluble glucocorticoid prodrugs, and in particular β-methasone hemisuccinate (BMS), for treatment of experimental cerebral malaria (ECM), using the murine P. berghei ANKA model. BMS is a novel derivative of the potent steroid β-methasone, and was specially synthesized to enable remote loading into nano-sterically stabilized liposomes (nSSL), to form nSSL-BMS. The novel nano-drug, composed of nSSL remote loaded with BMS, dramatically improves drug efficacy and abolishes the high toxicity seen upon administration of free BMS. nSSL-BMS reduces ECM rates in a dose-dependent manner and creates a survival time-window, enabling administration of an antiplasmodial drug, such as artemisone. Administration of artemisone after treatment with the nSSL-BMS results in complete cure. Treatment with BMS leads to lower levels of cerebral inflammation, demonstrated by changes in cytokines, chemokines, and cell markers, as well as diminished hemorrhage and edema, correlating with reduced clinical score. Administration of the liposomal formulation results in accumulation of BMS in the brains of sick mice but not of healthy mice. This steroidal nano-drug effectively eliminates the adverse effects of the cerebral syndrome even when the treatment is started at late stages of disease, in which disruption of the blood-brain barrier has occurred and mice show clear signs of neurological impairment. Overall, sequential treatment with nSSL-BMS and artemisone may be an efficacious and well-tolerated therapy for prevention of CM, elimination of parasites, and prevention of long-term cognitive damage.

  17. Steric Sea Level Trends in the Northeast Pacific Ocean: Possible Evidence of Global Sea Level Rise.

    NASA Astrophysics Data System (ADS)

    Thomson, Richard E.; Tabata, Susumu

    1989-06-01

    Thirty-year time series of hydrographic observations from Ocean Station PAPA and Line P' are used to estimate secular trends in monthly mean steric sea level heights relative to depths of 100 and 1000 decibars in the northeast Pacific Ocean. Linear trends at station P' (50°N, 145°W) indicate that steric heights relative to the 1000 db (approx. 1000 m) level are rising at a rate of 1.1 mm yr1, comparable with the Order 1 mm yr1 global trends suggested by analysis of selected long-term coastal tide gauge records. Approximately 67% of the increase in steric levels is due to thermosteric change at depths below 100 m, the smaller 33% contribution from the halosteric component apeasrs to be confined to the upper 100 m. Steric height trends at fine P' locations are also of order 1 mm yr1 but, in contrast to station P' trends, arise mainly through the halosteric component.Confidence levels for the linear trends an calculated in two ways. (i) using the Student-t test assuming that cub monthly observation is a statistically independent sample; and (ii) using the Student-t test in conjunction with the effective number of degrees of freedom derived from integral time scales. For station P', trends based on (i) are reliable to the 99% confidence level while for line P' only stations on the eastern portion of the fine have significant trends relative to the 1000 db level. Confidence levels obtained from (i) fail to take into consideration the long-term fluctuations in steric level records. To obtain more reliable estimates of the confidence intervals, we use integral time scales to determine the effective number of degrees of freedom for each monthly time series. Subsequent recalculation of trend-line confidence intervals indicates that the total steric height trends at Station P' remain significant at the 90% confidence level. The halosteric trend relative to 100 db is significant at 90% while the thermosteric trend relative to 1000 db is marginally significant at 70 to 80

  18. Surveying sterically demanding N-heterocyclic carbene ligands with restricted flexibility for palladium-catalyzed cross-coupling reactions.

    PubMed

    Würtz, Sebastian; Glorius, Frank

    2008-11-18

    Heterocyclic carbenes (NHCs), especially monodentate ones, have become the ligand of choice for many transition-metal-catalyzed transformations. They generally form highly stable complexes, have strong sigma-donor character, and have a unique shape that can be used to generate sterically demanding ligands.In this Account, we survey recent developments in the design and synthesis of some sterically demanding NHCs with a particularly strong influence on the metal's coordination sphere. We show the successful and insightful application of these ligands in transition-metal catalysis. First, we discuss methods for determining and classifying the electronic and steric properties of NHCs. In addition, we present data on the most important NHC ligands.The selective variation of either electronic or steric parameters of NHCs, and therefore of the catalyst, allows for the optimization of the reaction. Thus, we prepared several series of differentially substituted NHC derivatives. However, because the substituents varied were not directly connected to the carbene carbon, it was difficult to induce a large electronic variation. In contrast, an independent variation of the ligands' steric properties was more straightforward. We highlight three different classes of very sterically demanding NHCs that allow this kind of a steric variation: imidazo[1,5-a]pyridine-3-ylidenes, bioxazoline-derived carbenes (IBiox), and cyclic (alkyl)(amino)carbenes (CAAC).These latter NHC ligands can facilitate a number of challenging cross-coupling reactions. Successful transformations often require a monoligated palladium complex as the catalytically active species, and the sterically demanding NHC ligand favors this monoligated complex. In addition, the electron-rich NHC facilitates difficult oxidative addition steps. Moreover, the conformational flexibility of the ligands can facilitate the formation of catalytically active species and hemilabile interactions, such as agostic or anagostic bonds

  19. Math Is Like a Scary Movie? Helping Young People Overcome Math Anxiety

    ERIC Educational Resources Information Center

    Kulkin, Margaret

    2016-01-01

    Afterschool teachers who tutor students or provide homework help have a unique opportunity to help students overcome the social or emotional barriers that so often block learning. They can embrace a creative and investigative approach to math learning. Margaret Kulkin's interest in being a math attitude "myth-buster" led her to apply to…

  20. Steric sea level change in the Bay of Bengal: investigating the most variable component of sea level change

    NASA Astrophysics Data System (ADS)

    Uebbing, Bernd; Kusche, Jürgen; Rietbroek, Roelof; Shum, Ck

    2015-04-01

    Regional sea level change is influenced by contributions from mass sources, like melting of glaciers and the ice-sheets in Greenland and Antarctica, as well as steric contributions from changes in temperature and salinity of the oceans. Radar altimetry indicates a sea level trend in the Bay of Bengal of about 6 mm- yr over the time period of 2002-2014, which is significantly larger than the global mean trend. Here, we explain 80% of this rise by steric contributions and 20% by mass-related contributions. The increased rise of sea level in the Bay of Bengal threatens the coastal vulnerability of the surrounding countries like Bangladesh, where this effect is exacerbated in combination with land subsidence of the very low lying coastal areas. The BanD-AID (Bangladesh Delta: Assessment of the Causes of Sea-level Rise Hazards and Integrated Development of Predictive Modeling Towards Mitigation and Adaptation) project tries to assess the current and future sea level rise and its impacts on the people living in the threatened coastal areas. As a part of this, it is necessary to analyze the different mass and steric contributors to the total sea level rise to aid in the prediction of future risks. We use data from radar altimetry and the GRACE mission to separate the total sea level rise into contributions from mass sources and steric changes. In our approach, temporal GRACE gravity data and Jason-1 and -2 along track altimetry data are fitted to time invariant spatial patterns (fingerprints) to avoid problems with GRACE resolution, filtering, geocenter and related issues. Our results show that in the Bay of Bengal the steric component is influenced by annual and interannual phenomena and, at the same time, it is significantly larger compared to the individual mass contributions, which show a linear and relatively stable behavior over time. We validate the steric component of our inversion by comparing it to independent steric estimates from 4-D gridded temperature and

  1. Steric stabilization of Pickering emulsions for the efficient synthesis of polymeric microcapsules.

    PubMed

    Salari, Joris W O; van Heck, Jeroen; Klumperman, Bert

    2010-09-21

    It is commonly known that Pickering emulsions are extremely stable against coalescence and are, therefore, potentially interesting for the synthesis of new materials, such as colloidosomes, microcapsules, composite particles, foams, and so on. However, for the efficient synthesis of such materials, one also has to consider the colloidal stability against aggregation, which is often neglected. In this study, it is demonstrated that steric stabilization is provided to Pickering emulsion droplets by the adsorption of poly(styrene-block-ethylene-co-propylene) (pS-b-EP) and that it is a requirement for the efficient synthesis of polymeric microcapsules. Monodisperse polystyrene particles of 648 nm are synthesized by soap-free emulsion polymerization. A model Pickering emulsion is then formed by the addition of sodium chloride at a critical concentration of 325 mM and mixing it with either heptane or decane. Subsequently, pS-b-EP is added to the Pickering emulsion to provide steric stabilization. Size exclusion chromatography is used to prove and quantify the adsorption of pS-b-EP onto the Pickering emulsion droplets. A maximum surface coverage of 1.3 mg/m(2) is obtained after 2 h, which is approximately one-third of the adsorption on a pure pS surface. We believe that the presence of polar sulfate groups on the particle, which initially stabilized the particle in water, reduces the adsorption of pS-b-EP. Microcapsules are formed by heating the Pickering emulsion above the glass-transition temperature of the particles. Significant aggregation is observed, if no pS-b-EP is used. The adsorption of pS-b-EP provides steric stabilization to the Pickering emulsion droplets, reduces aggregation significantly, and ultimately leads to the successful and efficient synthesis of pS microcapsules.

  2. On the energetics of P-P bond dissociation of sterically strained tetraamino-diphosphanes.

    PubMed

    Blum, M; Puntigam, O; Plebst, S; Ehret, F; Bender, J; Nieger, M; Gudat, D

    2016-02-01

    The homolytic P-P bond fission in a series of sterically congested tetraaminodiphosphanes (R2N)2P-P(NR2)2 ({4}2-{9}2, two of which were newly synthesized and fully characterized) into diaminophosphanyl radicals (R2N)2P˙ (4-9) was monitored by VT EPR spectroscopy. Determination of the radical concentration from the EPR spectra permitted to calculate free dissociation energies ΔGDiss(295) as well as dissociation enthalpies ΔHDiss and entropies ΔSDiss, respectively. Large positive values of ΔGDiss(295) indicate that the degree of dissociation is in most cases low, and the concentration of persistent radicals--even if they are spectroscopically observable at ambient temperature--remains small. Appreciable dissociation was established only for the sterically highly congested acyclic derivative {9}2. Analysis of the trends in experimental data in connection with DFT studies indicate that radical formation is favoured by large entropy contributions and the energetic effect of structural relaxation (geometrical distortions and conformational changes in acyclic derivatives) in the radicals, and disfavoured by attractive dispersion forces. Comparison of the energetics of formation for CC-saturated N-heterocyclic diphosphanes and the 7π-radical 3c indicates that the effect of energetic stabilization by π-electron delocalization in the latter is visible, but stands back behind those of steric and entropic contributions. Evaluation of spectroscopic and computational data indicates that diaminophosphanyl radicals exhibit, in contrast to aminophosphenium cations, no strong energetic preference for a planar arrangement of the (R2N)2P unit. PMID:26337501

  3. Determining the Effective Density and Stabilizer Layer Thickness of Sterically Stabilized Nanoparticles

    PubMed Central

    2016-01-01

    A series of model sterically stabilized diblock copolymer nanoparticles has been designed to aid the development of analytical protocols in order to determine two key parameters: the effective particle density and the steric stabilizer layer thickness. The former parameter is essential for high resolution particle size analysis based on analytical (ultra)centrifugation techniques (e.g., disk centrifuge photosedimentometry, DCP), whereas the latter parameter is of fundamental importance in determining the effectiveness of steric stabilization as a colloid stability mechanism. The diblock copolymer nanoparticles were prepared via polymerization-induced self-assembly (PISA) using RAFT aqueous emulsion polymerization: this approach affords relatively narrow particle size distributions and enables the mean particle diameter and the stabilizer layer thickness to be adjusted independently via systematic variation of the mean degree of polymerization of the hydrophobic and hydrophilic blocks, respectively. The hydrophobic core-forming block was poly(2,2,2-trifluoroethyl methacrylate) [PTFEMA], which was selected for its relatively high density. The hydrophilic stabilizer block was poly(glycerol monomethacrylate) [PGMA], which is a well-known non-ionic polymer that remains water-soluble over a wide range of temperatures. Four series of PGMAx–PTFEMAy nanoparticles were prepared (x = 28, 43, 63, and 98, y = 100–1400) and characterized via transmission electron microscopy (TEM), dynamic light scattering (DLS), and small-angle X-ray scattering (SAXS). It was found that the degree of polymerization of both the PGMA stabilizer and core-forming PTFEMA had a strong influence on the mean particle diameter, which ranged from 20 to 250 nm. Furthermore, SAXS was used to determine radii of gyration of 1.46 to 2.69 nm for the solvated PGMA stabilizer blocks. Thus, the mean effective density of these sterically stabilized particles was calculated and determined to lie between 1.19 g

  4. Disentangling steric and electrostatic factors in nanoscale transport through confined space.

    PubMed

    Buchsbaum, Steven F; Mitchell, Nick; Martin, Hugh; Wiggin, Matt; Marziali, Andre; Coveney, Peter V; Siwy, Zuzanna; Howorka, Stefan

    2013-08-14

    The voltage-driven passage of biological polymers through nanoscale pores is an analytically, technologically, and biologically relevant process. Despite various studies on homopolymer translocation there are still several open questions on the fundamental aspects of pore transport. One of the most important unresolved issues revolves around the passage of biopolymers which vary in charge and volume along their sequence. Here we exploit an experimentally tunable system to disentangle and quantify electrostatic and steric factors. This new, fundamental framework facilitates the understanding of how complex biopolymers are transported through confined space and indicates how their translocation can be slowed down to enable future sensing methods.

  5. Sterically demanding hetero-substituted [2]borametallocenophanes of group IV metals: synthesis, structure and reactivity.

    PubMed

    Braunschweig, Holger; Dörfler, Rainer; Mies, Jan; Oechsner, Andreas

    2011-10-17

    We report the synthesis and characterisation of unprecedented unstrained [2]diborametallocenophanes of zirconium and hafnium that bear the bulky octamethylfluorenyl (η(5)-C(29)H(36)) system, the proligands of which were pre-constructed by a two-step synthesis. The compounds were fully characterised by NMR spectroscopy, MALDI-TOF mass spectrometry and X-ray diffraction analysis. Typical reactivities relevant to olefin polymerisation such as methylation and chloride abstraction were also investigated. Finally, a sterically demanding bis(octamethylfluorenyl) metallocene was prepared.

  6. Sterically controlled azomethine ylide cycloaddition polymerization of phenyl-C61-butyric acid methyl ester.

    PubMed

    Stephen, Meera; Ramanitra, Hasina H; Santos Silva, Hugo; Dowland, Simon; Bégué, Didier; Genevičius, Kristijonas; Arlauskas, Kęstutis; Juška, Gytis; Morse, Graham E; Distler, Andreas; Hiorns, Roger C

    2016-05-01

    Phenyl-C61-butyric acid methyl ester (PCBM) is polymerized simply using a one-pot reaction to yield soluble, high molecular weight polymers. The sterically controlled azomethine ylide cycloaddition polymerization (SACAP) is demonstrated to be highly adaptable and yields polymers with probable Mn≈ 24 600 g mol(-1) and Mw≈ 73 800 g mol(-1). Products are metal-free and of possible benefit to organic and hybrid photovoltaics and electronics as they form thin films from solution and have raised LUMOs. The promising electronic properties of this new polymer are discussed. PMID:27066898

  7. Steric interactions in cellular structures formed in a water/oil/surfactant/cosurfactant mixture.

    PubMed

    Molle, B; de Geyer, A; Guillermo, A; Farago, B

    2003-02-14

    Dynamics of dense microemulsion droplets forming ordered cellular phases as temperature increases are investigated by neutron spin echo spectroscopy (NSE). The shape fluctuations of droplets are shown using a specific contrast. Their relaxation time tau(f) is obtained by analysis of the NSE curves, which also reveals the short-range Brownian motion (diffusion constant D0) of the "caged" droplets. The thermal dependence of D0 and tau(f) supports the notion of entropically driven interdroplet steric repulsion stabilizing the cellular phases.

  8. Steric Interactions in Cellular Structures Formed in a Water/Oil/Surfactant/Cosurfactant Mixture

    NASA Astrophysics Data System (ADS)

    Molle, B.; de Geyer, A.; Guillermo, A.; Farago, B.

    2003-02-01

    Dynamics of dense microemulsion droplets forming ordered cellular phases as temperature increases are investigated by neutron spin echo spectroscopy (NSE). The shape fluctuations of droplets are shown using a specific contrast. Their relaxation time τf is obtained by analysis of the NSE curves, which also reveals the short-range Brownian motion (diffusion constant D0) of the “caged” droplets. The thermal dependence of D0 and τf supports the notion of entropically driven interdroplet steric repulsion stabilizing the cellular phases.

  9. Overcoming challenges to adoption of shared medical appointments.

    PubMed

    McCuistion, Mary Honodel; Stults, Cheryl D; Dohan, Daniel; Frosch, Dominick L; Hung, Dorothy Y; Tai-Seale, Ming

    2014-04-01

    Although research has shown many benefits of Shared Medical Appointments (SMAs) or group visits, uptake by physicians has been quite limited. The objective of this study was to explore the facilitators and barriers to implementing SMAs in a large multispecialty medical group. This was a comparative analysis of SMAs at 3 geographically distinct, semiautonomous divisions of the medical group based on qualitative themes identified in audio recorded key informant interviews with medical and administrative staff (n=12) involved with the implementation of SMAs. Data were collected by conducting key informant interviews focusing on the SMA implementation process, including motivations, history, barriers, and facilitators. Uptake at the 3 divisions was predicated by differing motivations, facilitators, and barriers. Divisions 1 and 2 allocated necessary resources including management support, a physician champion, expert consults, and support staff. These divisions also overcame physician reluctance and financial sustainability challenges. Despite early interest, Division 3 did not devote the time or resources to overcome initial resistance. Without the impetus of management mandate or a champion's enthusiasm, early attempts of SMA implementation faltered and were abandoned. In these cases, a physician champion, management support, and financial sustainability were judged to be the primary enablers of successful implementations of SMAs. Without these enablers and other contributing factors, implementing SMAs was challenging. PMID:24156662

  10. Barriers to HIV Cure.

    PubMed

    Stein, J; Storcksdieck Genannt Bonsmann, M; Streeck, H

    2016-10-01

    Since the beginning of the epidemic, more than 70 million people have been infected with human immunodeficiency virus (HIV) and about 38 million have died from acquired immune deficiency syndrome (AIDS)-related illnesses. While the discovery of highly active antiretroviral therapy (HAART) in the mid 90's has saved millions of lives, a complete eradication of HIV is still not possible as HIV can persist for decades in a small reservoir of latently infected cells. Once reactivated, these latently infected cells can actively produce viral particles. Recent studies suggest that several sanctuaries exist within infected individuals where HIV can remain undetected by the immune system. These cellular, anatomical and microanatomical viral reservoirs represent a major obstacle for the eradication of HIV. Here we review recent findings on potential sanctuaries of HIV and address potential avenues to overcome these immunological barriers. PMID:27620852

  11. How do strain and steric interactions affect the reactions of aromatic compounds with free radicals? Characterization of the radicals formed by muonium addition to p-xylene and [2.2]paracyclophane by DFT calculations and muon spin spectroscopy.

    PubMed

    McKenzie, Iain; Scheuermann, Robert; Sedlak, Kamil

    2012-07-26

    Muoniated radicals were produced by the addition of muonium (Mu) to the aromatic compound p-xylene (1) in the solid and liquid states and to the strained aromatic compound [2.2]paracyclophane (2) in the solid state. The radicals were characterized by avoided level crossing muon spin resonance spectroscopy and identified by comparing the experimentally determined muon hyperfine coupling constants with values obtained from DFT calculations. Mu was observed to add to both the secondary and tertiary carbons of 1, with the relative yield of the Mu adduct of the tertiary carbons estimated to be ∼10% in the liquid phase. The relative yield of the tertiary adduct is much higher in the solid state although this cannot be calculated exactly due to the overlap of resonances and the apparent nonuniform distribution of the radical orientations. There are three possible addition sites in 2 due to the lower symmetry of the six-membered ring compared with 1. Mu can add to the secondary carbons either from the outside of 2, generating the "exo" adduct, or from the inside, generating the "endo" adduct. The relative yields of the exo, endo, and tertiary carbon adducts are 67.1(1), 21.8(1), and 11.1(1)%, respectively. The barriers to Mu addition at the different sites of isolated molecules were determined from DFT calculations. The barriers for Mu addition to 2 are lower than the barriers for Mu addition to 1, except for addition to the "endo" position, where the unfavorable steric interactions with the second ring of 2 raise the addition barrier considerably. The measured relative yields do not reflect the distribution of products calculated using the activation energies obtained from the DFT calculations due to strong steric interactions with neighboring molecules.

  12. Barriers to Asthma Management as Identified by School Nurses.

    PubMed

    Quaranta, Judith E; Spencer, Gale A

    2016-10-01

    Asthma rates are increasing in children. School nurses have opportunities to care for children with asthma but need to overcome barriers impacting their ability to manage asthma in the school setting. This study (a) assessed barriers present in the school setting, (b) determined the impact of barriers on performance of asthma management behaviors, and (c) determined the impact of barriers on importance ratings of asthma management behaviors, asthma self-efficacy, and asthma attitudes (N = 537). Results revealed 72% of the nurses reported at least one barrier. As numbers of barriers increased, performance of asthma management behaviors decreased. Significant relationships were found between specific asthma management behaviors and specific barriers. No significant relationships were found between barriers and asthma self-efficacy, asthma attitude, or importance ratings of asthma management behaviors. Removing barriers may allow the nurse to perform at greatest effectiveness, enhancing the positive outcomes that result from appropriate asthma management. PMID:27044669

  13. Barriers vs Creativity in Translator Training

    ERIC Educational Resources Information Center

    Yazici, Mine

    2016-01-01

    This paper discusses translation problems awaiting Turkish students as well as the creative solutions they develop in overcoming them. It consists of two parts; The first part studies the barriers concerning translation procedures from the perspective of translation theory and Turkish translation history; The second parts analyses the impact of…

  14. Penetrating the Barriers to Teaching Higher Thinking.

    ERIC Educational Resources Information Center

    Supon, Viola

    1998-01-01

    Considers five ways to overcome barriers teachers face when they attempt to create thinking classrooms: (1) acquisition of conscious commitment; (2) legitimization of students' experiences; (3) integration of visualizing into the curriculum; (4) use of reflective analysis; and (5) diversification of perspectives. (SR)

  15. Elaboration of Sterically Stabilized Liposomes for S-Nitrosoglutathione Targeting to Macrophages.

    PubMed

    Diab, R; Virriat, A S; Ronzani, C; Fontanay, S; Grandemange, S; Elaissari, A; Foliguet, B; Maincent, P; Leroy, P; Duvaj, R E; Rihn, B H; Joubert, O

    2016-01-01

    S-nitrosoglutathione (GSNO) is a potential therapeutic for infectious disease treatment because of its pivotal role in macrophage-mediated inflammatory responses and host defense in addition to direct antibacterial activities. In this study, sterically stabilized cationic liposomes (SSCL) and sterically stabilized anionic liposomes (SSAL) were developed as nanocarriers for macrophage targeting. Elaborated liposomes were characterized in terms of size, zeta potential, morphology, encapsulation efficiency, in vitro drug release behavior and cytotoxicity. Their versatility in targeting monocytes/macrophages was determined by confocal laser scanning microscopy and transmission electron microscopy. Flow cytometry revealed that cellular uptake of both SSCL and SSAL was governed by several endocytic clathrin- and caveolae-dependent mechanisms. Quantitative assessments of intracellular nitric oxide demonstrated highly efficient uptake of GSNO-loaded SSCL that was twenty-fold higher than that of GSNO-free molecules. GSNO-loaded SSCL displayed strong bacteriostatic effects on Staphylococcus aureus and Pseudomonas aeruginosa, which can be involved in pulmonary infectious diseases. These results reveal the potential of liposomal GSNO as an anti-infective therapeutic due to its macrophage targeting capacity and direct antibacterial effects. PMID:27301185

  16. Steric selectivity in Na channels arising from protein polarization and mobile side chains.

    PubMed

    Boda, Dezso; Nonner, Wolfgang; Valiskó, Mónika; Henderson, Douglas; Eisenberg, Bob; Gillespie, Dirk

    2007-09-15

    Monte Carlo simulations of equilibrium selectivity of Na channels with a DEKA locus are performed over a range of radius R and protein dielectric coefficient epsilon(p). Selectivity arises from the balance of electrostatic forces and steric repulsion by excluded volume of ions and side chains of the channel protein in the highly concentrated and charged (approximately 30 M) selectivity filter resembling an ionic liquid. Ions and structural side chains are described as mobile charged hard spheres that assume positions of minimal free energy. Water is a dielectric continuum. Size selectivity (ratio of Na+ occupancy to K+ occupancy) and charge selectivity (Na+ to Ca2+) are computed in concentrations as low as 10(-5) M Ca2+. In general, small R reduces ion occupancy and favors Na+ over K+ because of steric repulsion. Small epsilon(p) increases occupancy and favors Na+ over Ca2+ because protein polarization amplifies the pore's net charge. Size selectivity depends on R and is independent of epsilon(p); charge selectivity depends on both R and epsilon(p). Thus, small R and epsilon(p) make an efficient Na channel that excludes K+ and Ca2+ while maximizing Na+ occupancy. Selectivity properties depend on interactions that cannot be described by qualitative or verbal models or by quantitative models with a fixed free energy landscape. PMID:17526571

  17. Chiral assembly of weakly curled hard rods: Effect of steric chirality and polarity

    SciTech Connect

    Wensink, H. H. Morales-Anda, L.

    2015-10-14

    We theoretically investigate the pitch of lyotropic cholesteric phases composed of slender rods with steric chirality transmitted via a weak helical deformation of the backbone. In this limit, the model is amenable to analytical treatment within Onsager theory and a closed expression for the pitch versus concentration and helical shape can be derived. Within the same framework, we also briefly review the possibility of alternative types of chiral order, such as twist-bend or screw-like nematic phases, finding that cholesteric order dominates for weakly helical distortions. While long-ranged or “soft” chiral forces usually lead to a pitch decreasing linearly with concentration, steric chirality leads to a much steeper decrease of quadratic nature. This reveals a subtle link between the range of chiral intermolecular interaction and the pitch sensitivity with concentration. A much richer dependence on the thermodynamic state is revealed for polar helices where parallel and anti-parallel pair alignments along the local director are no longer equivalent. It is found that weak temperature variations may lead to dramatic changes in the pitch, despite the lyotropic nature of the assembly.

  18. Role of water and steric constraints in the kinetics of cavity–ligand unbinding

    PubMed Central

    Tiwary, Pratyush; Mondal, Jagannath; Morrone, Joseph A.; Berne, B. J.

    2015-01-01

    A key factor influencing a drug’s efficacy is its residence time in the binding pocket of the host protein. Using atomistic computer simulation to predict this residence time and the associated dissociation process is a desirable but extremely difficult task due to the long timescales involved. This gets further complicated by the presence of biophysical factors such as steric and solvation effects. In this work, we perform molecular dynamics (MD) simulations of the unbinding of a popular prototypical hydrophobic cavity–ligand system using a metadynamics-based approach that allows direct assessment of kinetic pathways and parameters. When constrained to move in an axial manner, the unbinding time is found to be on the order of 4,000 s. In accordance with previous studies, we find that the cavity must pass through a region of sharp wetting transition manifested by sudden and high fluctuations in solvent density. When we remove the steric constraints on ligand, the unbinding happens predominantly by an alternate pathway, where the unbinding becomes 20 times faster, and the sharp wetting transition instead becomes continuous. We validate the unbinding timescales from metadynamics through a Poisson analysis, and by comparison through detailed balance to binding timescale estimates from unbiased MD. This work demonstrates that enhanced sampling can be used to perform explicit solvent MD studies at timescales previously unattainable, to our knowledge, obtaining direct and reliable pictures of the underlying physiochemical factors including free energies and rate constants. PMID:26371312

  19. Steric stabilization of "charge-free" cellulose nanowhiskers by grafting of poly(ethylene glycol).

    PubMed

    Araki, Jun; Mishima, Shiho

    2015-01-01

    A sterically stabilized aqueous suspension of "charge-free" cellulose nanowhiskers was prepared by hydrochloric acid hydrolysis of cotton powders and subsequent surface grafting of monomethoxy poly(ethylene glycol) (mPEG). The preparation scheme included carboxylation of the terminal hydroxyl groups in mPEG via oxidation with silica gel particles carrying 2,2,6,6-tetramethyl-1-pyperidinyloxyl (TEMPO) moieties and subsequent esterification between terminal carboxyls in mPEG and surface hydroxyl groups of cellulose nanowhiskers, mediated by 1,1'-carbonyldiimidazole (CDI) in dimethyl sulfoxide or dimethylacetamide. Some of the prepared PEG-grafted samples showed remarkable flow birefringence and enhanced stability after 24 h, even in 0.1 M NaCl, suggesting successful steric stabilization by efficient mPEG grafting. Actual PEG grafting via ester linkages was confirmed by attenuated total reflectance-Fourier transform infrared spectrometry. In a typical example, the amount of grafted mPEG was estimated as ca. 0.3 g/g cellulose by two measurements, i.e., weight increase after grafting and weight loss after alkali cleavage of ester linkages. Transmission electron microscopy indicated unchanged nanowhisker morphology after mPEG grafting. PMID:25547722

  20. Influence of steric interactions on the dielectric and electrokinetic properties in colloidal suspensions.

    PubMed

    López-García, José Juan; Horno, José; Grosse, Constantino

    2015-11-15

    One of the main assumptions of the standard electrokinetic model is that ions behave as point like entities. In this work we remove this assumption and analyze the main consequences of finite ionic size on the dielectric and electrokinetic properties of colloidal suspensions. We represent the steric interactions by means of the Bikerman and the Carnahan-Starling equations and solve numerically the standard linearized electrokinetic equations in the stationary and the frequency domains, for surface charge density and electrolyte solution concentration values typically encountered in colloidal suspensions. In all cases the steric interactions improve upon the predictions of the standard model since the surface potential, the electrophoretic mobility, and the conductivity and permittivity increments increase. However, the corrections introduced by the Bikerman equation are generally small: less than 10% as compared to the standard model. On the contrary, the Carnahan-Starling equation leads to corrections to the surface potential versus surface charge and the electrophoretic mobility values that easily surpass 10% and can attain values as high as 50%. Corrections to the conductivity and permittivity increments are smaller but still non negligible.

  1. Modeling multivalent ligand-receptor interactions with steric constraints on configurations of cell surface receptor aggregates

    SciTech Connect

    Monine, Michael; Posner, Richard; Savage, Paul; Faeder, James; Hlavacek, William S

    2008-01-01

    Signal transduction generally involves multivalent protein-protein interactions, which can produce various protein complexes and post-translational modifications. The reaction networks that characterize these interactions tend to be so large as to challenge conventional simulation procedures. To address this challenge, a kinetic Monte Carlo (KMC) method has been developed that can take advantage of a model specification in terms of reaction rules for molecular interactions. A set of rules implicitly defines the reactions that can occur as a result of the interactions represented by the rules. With the rule-based KMC method, explicit generation of the underlying chemical reaction network implied by rules is avoided. Here, we apply and extend this method to characterize the interactions of a trivalent ligand with a bivalent cell-surface receptor. This system is also studied experimentally. We consider the following kinetic models: an equivalent-site model, an extension of this model, which takes into account steric constraints on the configurations of receptor aggregates, and finally, a model that accounts for cyclic receptor aggregates. Simulation results for the equivalent-site model are consistent with an equilibrium continuum model. Using these models, we investigate the effects of steric constraints and the formation of cyclic aggregates on the kinetics and equilibria of small and large aggregate formation and the percolation phase transition that occurs in this system.

  2. A family of reworkable polymer networks by the incorporation of sterically hindered urea linkages

    NASA Astrophysics Data System (ADS)

    Malik, Jitendra

    2002-01-01

    Crosslinked polymer networks are excellent materials for multiple applications. However, while their crosslinked structure gives the networks many positive attributes, it also makes them essentially intractable after the covalent crosslinks are formed. Therefore, it is exceedingly difficult to reprocess polymer networks once crosslinked without exposure to extreme degradation conditions. The first part of this work focuses in creating crosslinked networks that could show controlled disassembly upon stimulus. It was found that a controlled network disassembly process could be invoked by the incorporation of sterically hindered urea linkages into the polymer network. This network was shown to disassemble upon exposure to heat, whereas in the absence of heat, the network was found to maintain its crosslinked structure. The disassembly temperature could be varied by careful selection of the cleaving agent based on controllable considerations. This work focuses on showing controlled network disassembly of a crosslinked polymer matrix. Herein, we describe the factors that control the disassembly temperature and conclude with a possible mechanism for the disassembly process based on experimental data. Once disassembly could be shown to occur using sterically hindered urea linkages, polymer molecules were incorporated directly into the reworkable network. The presence of the polymer was found to significantly effect the reworkable behavior and these effects were detailed and an explanation for the behavior was provided. The work then focused on the effects of sterics along the length of the reworkable crosslinker. It was found that sterics along the length of the chain did have an effect. Specifically, as the steric hindrance increased around the urea linkage the rework temperature was found to decrease. Our focus then shifted to study the effects of changing the number of reworkable linkages per crosslinker. As the number per crosslinker changed from two to one the

  3. Designing a hydrophobic barrier within biomimetic nanopores.

    PubMed

    Trick, Jemma L; Wallace, E Jayne; Bayley, Hagan; Sansom, Mark S P

    2014-11-25

    Nanopores in membranes have a range of potential applications. Biomimetic design of nanopores aims to mimic key functions of biological pores within a stable template structure. Molecular dynamics simulations have been used to test whether a simple β-barrel protein nanopore can be modified to incorporate a hydrophobic barrier to permeation. Simulations have been used to evaluate functional properties of such nanopores, using water flux as a proxy for ionic conductance. The behavior of these model pores has been characterized as a function of pore size and of the hydrophobicity of the amino acid side chains lining the narrow central constriction of the pore. Potential of mean force calculations have been used to calculate free energy landscapes for water and for ion permeation in selected models. These studies demonstrate that a hydrophobic barrier can indeed be designed into a β-barrel protein nanopore, and that the height of the barrier can be adjusted by modifying the number of consecutive rings of hydrophobic side chains. A hydrophobic barrier prevents both water and ion permeation even though the pore is sterically unoccluded. These results both provide insights into the nature of hydrophobic gating in biological pores and channels, and furthermore demonstrate that simple design features may be computationally transplanted into β-barrel membrane proteins to generate functionally complex nanopores.

  4. Promoting Physical Activity: Addressing Barriers and Moving Forward

    ERIC Educational Resources Information Center

    Beighle, Aaron; Morrow, James R.

    2014-01-01

    The barriers that keep individuals from adopting and maintaining active lifestyles are very complex. Strategies for overcoming these barriers and to incentivize and assist inactive individuals to benefit from physical activity are necessary. In addition, it is important to examine the impact of public policy on active living. As youth physical…

  5. The Gendered International School: Barriers to Women Managers' Progression

    ERIC Educational Resources Information Center

    Sanderson, Ruth Elizabeth; Whitehead, Stephen

    2016-01-01

    Purpose: The purpose of this paper is to examine the barriers women identify to their promotion in international schools and also the ways in which women can overcome these barriers. Design/methodology/approach: The field of enquiry is international schools, with the study drawing on qualitative research. The researchers interviewed 11 women from…

  6. Viruses Challenge Selectivity Barrier of Nuclear Pores

    PubMed Central

    Labokha, Aksana A.; Fassati, Ariberto

    2013-01-01

    Exchange between the nucleus and the cytoplasm occurs through nuclear pore complexes (NPCs) embedded in the double membrane of the nuclear envelope. NPC permeability barrier restricts the entry of inert molecules larger than 5 nm in diameter but allows facilitated entry of selected cargos, whose size can reach up to 39 nm. The translocation of large molecules is facilitated by nuclear transport receptors (NTRs) that have affinity to proteins of NPC permeability barrier. Viruses that enter the nucleus replicate evolved strategies to overcome this barrier. In this review, we will discuss the functional principles of NPC barrier and nuclear transport machinery, as well as the various strategies viruses use to cross the selective barrier of NPCs. PMID:24084236

  7. Assessment in the competition between steric and electronic effects in the elimination kinetic of hydrogen in 1,4-cyclohexadienes in the gas phase. Quantum chemical theory calculations

    NASA Astrophysics Data System (ADS)

    Ramírez, Beatriz; Córdova-Sintjago, Tania C.; Ruette, Fernando; Chuchani, Gabriel

    2015-02-01

    The mechanisms of gas-phase thermal decomposition of alkyl-substituted cyclohexadienes were studied by the means of quantum chemical calculations with theory levels Møller-Plesset pertubation theory (MP2) and density functional theory (DFT) (B3LYP, MPW1PW91, PBEPBE, ωB97XD, CAM-B3LYP, M06, and M062X) with 6-31G(d,p), 6-31++G(d,p) basis sets. The examination of the reaction pathways of each substrate demonstrated a molecular mechanism through six-membered cyclic boat-like transition state (TS) structure. An alkyl group substituent causes a detrimental effect on the reaction rate, compared to the parent compound 1,4-cyclohexadiene; however, the reaction was favoured in the case of 3,6-dimethyl substitution. The 3,6-dimethyl-1,4-cyclohexadiene compound has activation energy 11.2 kJ/mol lower than the reference compound, which overcomes the effect of the most negative entropy of activation in the series. The effects of alkyl substituents in these reactions suggest a complex combination of electronic and steric influence. These reactions are characterised as highly synchronous concerted, with small predominance of C-H bond breaking in the TS.

  8. Functional metal-organic frameworks via ligand doping: influences of ligand charge and steric demand.

    PubMed

    Wang, Cheng; Liu, Demin; Xie, Zhigang; Lin, Wenbin

    2014-02-01

    Doping a functional ligand into a known crystalline system built from ligands of similar shape and length provides a powerful strategy to construct functional metal-organic frameworks (MOFs) with desired functionality and structural topology. This mix-and-match approach mimics the widely applied metal ion doping (or solid solution formation) in traditional inorganic materials, such as metal oxides, wherein maintaining charge balance of the doped lattice and ensuring size match between doped metal ions and the parent lattice are key to successful doping. In this work, we prepared three sterically demanding dicarboxylate ligands based on Ir/Ru-phosphors with similar structures and variable charges (-2 to 0), [Ir(ppy)3]-dicarboxylate (L1, ppy is 2-phenylpyridine), [Ir(bpy)(ppy)2](+)-dicarboxylate (L2, bpy is 2,2'-bipyridine), and Ru(bpy)3](2+)-dicarboxylate (L3), and successfully doped them into the known IRMOF-9/-10 structures by taking advantage of matching length between 4,4'-biphenyl dicarboxylate (BPDC) and L1-L3. We systematically investigated the effects of size and charge of the doping ligand on the MOF structures and the ligand doping levels in these MOFs. L1 carries a -2 charge to satisfy the charge requirement of the parent Zn4O(BPDC)3 framework and can be mixed into the IRMOF-9/-10 structure in the whole range of H2L1/H2BPDC ratios from 0 to 1. The steric bulk of L1 induces a phase transition from the interpenetrated IRMOF-9 structure to the non-interpenetrated IRMOF-10 counterpart. L2 and L3 do not match the dinegative charge of BPDC in order to maintain the charge balance for a neutral IRMOF-9/-10 framework and can only be doped into the IRMOF-9 structure to a certain degree. L2 and L3 form a charge-balanced new phase with a neutral framework structure at higher doping levels (>8% For L2 and >6% For L3). This systematic investigation reveals the influences of steric demand and charge balance on ligand doping in MOFs, a phenomenon that has been well

  9. Steric parameters, molecular modeling and hydropathic interaction analysis of the pharmacology of para-substituted methcathinone analogues

    PubMed Central

    Sakloth, F; Kolanos, R; Mosier, P D; Bonano, J S; Banks, M L; Partilla, J S; Baumann, M H; Negus, S S; Glennon, R A

    2015-01-01

    Background and Purpose There is growing concern over the abuse of certain psychostimulant methcathinone (MCAT) analogues. This study extends an initial quantitative structure–activity relationship (QSAR) investigation that demonstrated important steric considerations of seven 4- (or para-)substituted analogues of MCAT. Specifically, the steric character (Taft's steric ES) of the 4-position substituent affected in vitro potency to induce monoamine release via dopamine and 5-HT transporters (DAT and SERT) and in vivo modulation of intracranial self-stimulation (ICSS). Here, we have assessed the effects of other steric properties of the 4-position substituents. Experimental Approach Definitive steric parameters that more explicitly focus on the volume, width and length of the MCAT 4-position substituents were assessed. In addition, homology models of human DAT and human SERT based upon the crystallized Drosophila DAT were constructed and docking studies were performed, followed by hydropathic interaction (HINT) analysis of the docking results. Key Results The potency of seven MCAT analogues at DAT was negatively correlated with the volume and maximal width of their 4-position substituents, whereas potency at SERT increased as substituent volume and length increased. SERT/DAT selectivity, as well as abuse-related drug effects in the ICSS procedure, also correlated with the same parameters. Docking solutions offered a means of visualizing these findings. Conclusions and Implications These results suggest that steric aspects of the 4-position substituents of MCAT analogues are key determinants of their action and selectivity, and that the hydrophobic nature of these substituents is involved in their potency at SERT. PMID:25522019

  10. Multinuclear oxo-bridged manganese complexes with a bulky substituted benzoate ligand: novel species obtained by using steric control.

    PubMed

    Mukhopadhyay, Sumitra; Armstrong, William H

    2003-10-29

    A sterically hindered carboxylate ligand is used to synthesize the first transition metal complex containing both bis-mu-oxo and bis-mu-carboxylato groups, [Mn2(mu-O)2(mu-ArtolCO2)2(bpy)2]+. However, methyl substitution on the chelating bipyridine ligand results in the formation of a strikingly different and novel hexanuclear species, [Mn6(mu-O)4(mu3-O)4(mu-ArtolCO2)2(dmb)6]4+. Steric interactions between the bridging carboxylates and chelating pyridine-based ligands determine the nuclearity of the complexes formed.

  11. Barrier Formation

    PubMed Central

    Lyaruu, D.M.; Medina, J.F.; Sarvide, S.; Bervoets, T.J.M.; Everts, V.; DenBesten, P.; Smith, C.E.; Bronckers, A.L.J.J.

    2014-01-01

    Enamel fluorosis is an irreversible structural enamel defect following exposure to supraoptimal levels of fluoride during amelogenesis. We hypothesized that fluorosis is associated with excess release of protons during formation of hypermineralized lines in the mineralizing enamel matrix. We tested this concept by analyzing fluorotic enamel defects in wild-type mice and mice deficient in anion exchanger-2a,b (Ae2a,b), a transmembrane protein in maturation ameloblasts that exchanges extracellular Cl− for bicarbonate. Defects were more pronounced in fluorotic Ae2a,b−/− mice than in fluorotic heterozygous or wild-type mice. Phenotypes included a hypermineralized surface, extensive subsurface hypomineralization, and multiple hypermineralized lines in deeper enamel. Mineral content decreased in all fluoride-exposed and Ae2a,b−/− mice and was strongly correlated with Cl−. Exposure of enamel surfaces underlying maturation-stage ameloblasts to pH indicator dyes suggested the presence of diffusion barriers in fluorotic enamel. These results support the concept that fluoride stimulates hypermineralization at the mineralization front. This causes increased release of protons, which ameloblasts respond to by secreting more bicarbonates at the expense of Cl− levels in enamel. The fluoride-induced hypermineralized lines may form barriers that impede diffusion of proteins and mineral ions into the subsurface layers, thereby delaying biomineralization and causing retention of enamel matrix proteins. PMID:24170372

  12. Sterically stabilized liposomes as a carrier for alpha-emitting radium and actinium radionuclides.

    PubMed

    Henriksen, Gjermund; Schoultz, B W; Michaelsen, T E; Bruland, Ø S; Larsen, R H

    2004-05-01

    The alpha-particle emitting radionuclides (223)Ra (t(1/2) = 11.4 d), (224)Ra (t(1/2) = 3.6 d), and (225)Ac(t(1/2) = 10.0 d) may have a broad application in targeted radiotherapy provided that they could be linked to vehicles with tumor affinity. The potential usefulness of liposomes as carriers was studied in the present work. Radium and actinium radionuclides could be loaded in good yields into sterically stabilized liposomes. Subsequent coating of the liposomes with a folate-F(ab')(2) construct yielded a product with affinity towards tumor cells expressing folate receptors. Radionuclide loaded liposomes showed excellent stability in serum in vitro.

  13. A Steric Antagonism of Actin Polymerization by a Salmonella Virulence Protein

    SciTech Connect

    Margarit,S.; Davidson, W.; Frego, L.; Stebbins, F.

    2006-01-01

    Salmonella spp. require the ADP-ribosyltransferase activity of the SpvB protein for intracellular growth and systemic virulence. SpvB covalently modifies actin, causing cytoskeletal disruption and apoptosis. We report here the crystal structure of the catalytic domain of SpvB, and we show by mass spectrometric analysis that SpvB modifies actin at Arg177, inhibiting its ATPase activity. We also describe two crystal structures of SpvB-modified, polymerization-deficient actin. These structures reveal that ADP-ribosylation does not lead to dramatic conformational changes in actin, suggesting a model in which this large family of toxins inhibits actin polymerization primarily through steric disruption of intrafilament contacts.

  14. A steric tethering approach enables palladium-catalysed C-H activation of primary amino alcohols.

    PubMed

    Calleja, Jonas; Pla, Daniel; Gorman, Timothy W; Domingo, Victoriano; Haffemayer, Benjamin; Gaunt, Matthew J

    2015-12-01

    Aliphatic primary amines are a class of chemical feedstock essential to the synthesis of higher-order nitrogen-containing molecules, commonly found in biologically active compounds and pharmaceutical agents. New methods for the construction of complex amines remain a continuous challenge to synthetic chemists. Here, we outline a general palladium-catalysed strategy for the functionalization of aliphatic C-H bonds within amino alcohols, an important class of small molecule. Central to this strategy is the temporary conversion of catalytically incompatible primary amino alcohols into hindered secondary amines that are capable of undergoing a sterically promoted palladium-catalysed C-H activation. Furthermore, a hydrogen bond between amine and catalyst intensifies interactions around the palladium and orients the aliphatic amine substituents in an ideal geometry for C-H activation. This catalytic method directly transforms simple, easily accessible amines into highly substituted, functionally concentrated and structurally diverse products, and can streamline the synthesis of biologically important amine-containing molecules.

  15. Chemiluminescence efficiency of catalyzed 1,2-dioxetanone decomposition determined by steric effects.

    PubMed

    Bartoloni, Fernando Heering; de Oliveira, Marcelo Almeida; Ciscato, Luiz Francisco Monteiro Leite; Augusto, Felipe Alberto; Bastos, Erick Leite; Baader, Wilhelm Josef

    2015-04-17

    The chemiluminescent decomposition of 1,2-dioxetanones (α-peroxylactones), catalyzed by an appropriate fluorescent activator, is an important simple model for efficient bioluminescent transformations. In this work, we report experimental data on the catalyzed decomposition of two spiro-substituted 1,2-dioxetanone derivatives, which support the occurrence of an intermolecular electron transfer from the activator to the peroxide. The low efficiency of the studied systems is associated with steric hindrance during the chemiexcitation sequence, rationalized using the concept of supermolecule formation between the peroxide and the catalyst. This approach explains the difference in the chemiexcitation efficiencies in the decomposition of four-membered cyclic peroxide derivatives: 1,2-dioxetanes, 1,2-dioxetanones, and 1,2-dioxetanedione (the intermediate in the peroxyoxalate reaction), which are the most important model compounds for excited-state formation in chemiluminescence and bioluminescence processes. PMID:25831218

  16. Steric trapping reveals a cooperativity network in the intramembrane protease GlpG

    PubMed Central

    Yang, Zhongyu; Kim, Miyeon; Sungsuwan, Suttipun; Huang, Xuefei; Hubbell, Wayne L.; Hong, Heedeok

    2016-01-01

    Membrane proteins are assembled through balanced interactions among protein, lipids and water. Studying their folding while maintaining the native lipid environment is necessary but challenging. Here we present methods for analyzing key elements in membrane protein folding including thermodynamic stability, compactness of the unfolded state and folding cooperativity under native conditions. The methods are based on steric trapping which couples unfolding of a doubly-biotinylated protein to binding of monovalent streptavidin (mSA). We further advanced this technology for general application by developing versatile biotin probes possessing spectroscopic reporters that are sensitized by mSA binding or protein unfolding. By applying these methods to an intramembrane protease GlpG of Escherichia coli, we elucidated a widely unraveled unfolded state, subglobal unfolding of the region encompassing the active site, and a network of cooperative and localized interactions to maintain the stability. These findings provide crucial insights into the folding energy landscape of membrane proteins. PMID:26999782

  17. Sterically stabilized liposomes as a carrier for alpha-emitting radium and actinium radionuclides.

    PubMed

    Henriksen, Gjermund; Schoultz, B W; Michaelsen, T E; Bruland, Ø S; Larsen, R H

    2004-05-01

    The alpha-particle emitting radionuclides (223)Ra (t(1/2) = 11.4 d), (224)Ra (t(1/2) = 3.6 d), and (225)Ac(t(1/2) = 10.0 d) may have a broad application in targeted radiotherapy provided that they could be linked to vehicles with tumor affinity. The potential usefulness of liposomes as carriers was studied in the present work. Radium and actinium radionuclides could be loaded in good yields into sterically stabilized liposomes. Subsequent coating of the liposomes with a folate-F(ab')(2) construct yielded a product with affinity towards tumor cells expressing folate receptors. Radionuclide loaded liposomes showed excellent stability in serum in vitro. PMID:15093814

  18. Effect of Structural Modifications on the Self-Assembly of Oligoprolines Conjugated with Sterically Demanding Chromophores.

    PubMed

    Lewandowska, Urszula; Zajaczkowski, Wojciech; Pisula, Wojciech; Ma, Yingjie; Li, Chen; Müllen, Klaus; Wennemers, Helma

    2016-03-01

    Conjugates between oligoprolines and sterically demanding perylene monoimides (PMIs) form hierarchical supramolecular self-assemblies. The influence of the length and stereochemistry at the attachment site between the peptide backbone and the chromophore on the self-assembly properties of the conjugates was explored. Comparison between oligoprolines bearing 4R- or 4S-configured azidoprolines (Azp) for the conjugation with the PMIs revealed that diastereoisomers with 4R configuration guide the self-assembly consistently better than conjugates with 4S configuration. Elongating the peptide chain beyond nine proline residues or introducing structural "errors", by altering the absolute configuration of one stereogenic center at the outside of the functionalizable oligoproline helix, lowered the efficacy of self-assembly significantly, both in solution phase and in the solid state. The results showed how subtle structural modifications allow for tuning the self-assembly of chromophores and provided further design principles for the development of peptide-chromophore conjugates into nanostructured materials.

  19. Enantiospecific photoresponse of sterically hindered diarylethenes for chiroptical switches and photomemories

    NASA Astrophysics Data System (ADS)

    Li, Wenlong; Li, Xin; Xie, Yongshu; Wu, Yue; Li, Mengqi; Wu, Xin-Yan; Zhu, Wei-Hong; Tian, He

    2015-03-01

    Light-driven transcription, replication and enzyme catalysis are critically dependent upon a delicate transfer between molecular and supramolecular chirality. Chemists have well realized the impressive stereospecificity over many thermally accessible cycloaddition with chiral catalysts, but making light work in the enantiomer control of diarylethene photocyclization has proved to be more challenging. Here, we report a unique sterically hindered diarylethene (BBTE) system with absolute enantiospecific photocyclization and cycloreversion. Moreover, we have fully separated all the five thermally stable isomers, consisting of one achiral parallel conformer, one pair of anti-parallel ring-open enantiomers, and another pair of ring-closed enantiomers, whose absolute chiral configurations are entirely elucidated by single X-ray crystallographic analyses. The photo-responsive feature exhibits a reversible, complete enantio-control transformation without racemism, offering an unrivaled unimolecular enantiospecific platform for potential applications as bistable chiroptical switches and all-photonic photomemories with optical rotation as non-destructive readout.

  20. Preparation of metallic cation conducting polymers based on sterically hindered phenols containing polymeric systems

    DOEpatents

    Skotheim, Terje A.; Okamoto, Yoshiyuki; Lee, Hung S.

    1989-01-01

    The present invention relates to ion-conducting solvent-free polymeric systems characterized as being cationic single ion conductors. The solvent-free polymer electrolytes comprise a flexible polymer backbone to which is attached a metal salt, such as a lithium, sodium or potassium salt, of a sterically hindered phenol. The solid polymer electrolyte may be prepared either by (1) attaching the hindered phenol directly to a flexible polymeric backbone, followed by neutralization of the phenolic OH's or (2) reacting the hindered phenol with a polymer precursor which is then polymerized to form a flexible polymer having phenolic OH's which are subsequently neutralized. Preferably the hindered phenol-modified polymeric backbone contains a polyether segment. The ionic conductivity of these solvent-free polymer electrolytes has been measured to be in the range of 10.sup.-4 to 10.sup.-7 S cm.sup.-1 at room temperature.

  1. Preparation of metallic cation conducting polymers based on sterically hindered phenols containing polymeric systems

    DOEpatents

    Skotheim, T.A.; Okamoto, Yoshiyuki; Lee, H.S.

    1989-11-21

    The present invention relates to ion-conducting solvent-free polymeric systems characterized as being cationic single ion conductors. The solvent-free polymer electrolytes comprise a flexible polymer backbone to which is attached a metal salt, such as a lithium, sodium or potassium salt, of a sterically hindered phenol. The solid polymer electrolyte may be prepared either by (1) attaching the hindered phenol directly to a flexible polymeric backbone, followed by neutralization of the phenolic OH's or (2) reacting the hindered phenol with a polymer precursor which is then polymerized to form a flexible polymer having phenolic OH's which are subsequently neutralized. Preferably the hindered phenol-modified polymeric backbone contains a polyether segment. The ionic conductivity of these solvent-free polymer electrolytes has been measured to be in the range of 10[sup [minus]4] to 10[sup [minus]7] S cm[sup [minus]1] at room temperature.

  2. New synthetic amphiphilic polymers for steric protection of liposomes in vivo.

    PubMed

    Torchilin, V P; Trubetskoy, V S; Whiteman, K R; Caliceti, P; Ferruti, P; Veronese, F M

    1995-09-01

    Carboxy group-terminated synthetic polymers--branched poly(ethylene glycol), poly(acryloylmorpholine), and poly(vinylpyrrolidone)--were made amphiphilic by derivatization with phosphatidyl ethanolamine via the terminal carboxy group and then incorporated into lecithin-cholesterol liposomes prepared by the detergent dialysis method. Following the biodistribution of liposomes in mice, all three polymers were shown to be effective steric protectors for liposomes and were able to sharply increase liposome circulation times in a concentration-dependent manner. The accumulation of liposomes in the liver decreases. The effects observed are similar to those found for liposomes modified with linear poly(ethylene glycol). At low polymer concentration, amphiphilic branched poly(ethylene glycol) seems to be the most effective liposome protector, most probably, because at the same molar content of anchoring groups, each attachment point carries two polymeric chains and doubles the quantity of liposome-grafted polymer comparing to linear poly(ethylene glycol).

  3. A steric tethering approach enables palladium-catalysed C-H activation of primary amino alcohols

    NASA Astrophysics Data System (ADS)

    Calleja, Jonas; Pla, Daniel; Gorman, Timothy W.; Domingo, Victoriano; Haffemayer, Benjamin; Gaunt, Matthew J.

    2015-12-01

    Aliphatic primary amines are a class of chemical feedstock essential to the synthesis of higher-order nitrogen-containing molecules, commonly found in biologically active compounds and pharmaceutical agents. New methods for the construction of complex amines remain a continuous challenge to synthetic chemists. Here, we outline a general palladium-catalysed strategy for the functionalization of aliphatic C-H bonds within amino alcohols, an important class of small molecule. Central to this strategy is the temporary conversion of catalytically incompatible primary amino alcohols into hindered secondary amines that are capable of undergoing a sterically promoted palladium-catalysed C-H activation. Furthermore, a hydrogen bond between amine and catalyst intensifies interactions around the palladium and orients the aliphatic amine substituents in an ideal geometry for C-H activation. This catalytic method directly transforms simple, easily accessible amines into highly substituted, functionally concentrated and structurally diverse products, and can streamline the synthesis of biologically important amine-containing molecules.

  4. Anti-amyloid precursor protein immunoglobulins inhibit amyloid-β production by steric hindrance.

    PubMed

    Thomas, Rhian S; Liddell, J Eryl; Kidd, Emma J

    2011-01-01

    The cleavage of amyloid precursor protein (APP) by β- and γ-secretases results in the production of amyloid-β (Aβ) in Alzheimer's disease. We raised two monoclonal antibodies, 2B3 and 2B12, that recognize the β-secretase cleavage site on APP but not Aβ. We hypothesized that these antibodies would reduce Aβ levels via steric hindrance of β-secretase. Both antibodies decreased extracellular Aβ levels from astrocytoma cells, but 2B3 was more potent than 2B12. Levels of soluble sAPPα from the nonamyloidogenic α-secretase pathway and intracellular APP were not affected by either antibody nor were there any effects on cell viability. 2B3 exhibited a higher affinity for APP than 2B12 and its epitope appeared to span the cleavage site, whereas 2B12 bound slightly upstream. Both of these factors probably contribute to its greater effect on Aβ levels. After 60 min incubation at pH 4.0, most 2B3 and 2B12 remained bound to their antigen, suggesting that the antibodies will remain bound to APP in the acidic endosomes where β-secretase cleavage probably occurs. Only 2B3 and 2B12, but not control antibodies, inhibited the cleavage of sAPPα by β-secretase in a cell-free assay where the effects of antibody internalization and intracellular degradation were excluded. 2B3 virtually abolished this cleavage. In addition, levels of C-terminal APP fragments, generated following β-secretase cleavage (βCTF), were significantly reduced in cells after incubation with 2B3. These results strongly suggest that anti-cleavage site IgGs can generically reduce Aβ levels via inhibition of β-secretase by steric hindrance and may provide a novel alternative therapy for Alzheimer's disease.

  5. RNABC: forward kinematics to reduce all-atom steric clashes in RNA backbone.

    PubMed

    Wang, Xueyi; Kapral, Gary; Murray, Laura; Richardson, David; Richardson, Jane; Snoeyink, Jack

    2008-01-01

    Although accurate details in RNA structure are of great importance for understanding RNA function, the backbone conformation is difficult to determine, and most existing RNA structures show serious steric clashes (>or= 0.4 A overlap) when hydrogen atoms are taken into account. We have developed a program called RNABC (RNA Backbone Correction) that performs local perturbations to search for alternative conformations that avoid those steric clashes or other local geometry problems. Its input is an all-atom coordinate file for an RNA crystal structure (usually from the MolProbity web service), with problem areas specified. RNABC rebuilds a suite (the unit from sugar to sugar) by anchoring the phosphorus and base positions, which are clearest in crystallographic electron density, and reconstructing the other atoms using forward kinematics. Geometric parameters are constrained within user-specified tolerance of canonical or original values, and torsion angles are constrained to ranges defined through empirical database analyses. Several optimizations reduce the time required to search the many possible conformations. The output results are clustered and presented to the user, who can choose whether to accept one of the alternative conformations. Two test evaluations show the effectiveness of RNABC, first on the S-motifs from 42 RNA structures, and second on the worst problem suites (clusters of bad clashes, or serious sugar pucker outliers) in 25 unrelated RNA structures. Among the 101 S-motifs, 88 had diagnosed problems, and RNABC produced clash-free conformations with acceptable geometry for 71 of those (about 80%). For the 154 worst problem suites, RNABC proposed alternative conformations for 72. All but 8 of those were judged acceptable after examining electron density (where available) and local conformation. Thus, even for these worst cases, nearly half the time RNABC suggested corrections suitable to initiate further crystallographic refinement. The program is

  6. The effects of aggressive mitigation on steric sea level rise and sea ice changes

    NASA Astrophysics Data System (ADS)

    Körper, J.; Höschel, I.; Lowe, J. A.; Hewitt, C. D.; Salas y Melia, D.; Roeckner, E.; Huebener, H.; Royer, J.-F.; Dufresne, J.-L.; Pardaens, A.; Giorgetta, M. A.; Sanderson, M. G.; Otterå, O. H.; Tjiputra, J.; Denvil, S.

    2013-02-01

    With an increasing political focus on limiting global warming to less than 2 °C above pre-industrial levels it is vital to understand the consequences of these targets on key parts of the climate system. Here, we focus on changes in sea level and sea ice, comparing twenty-first century projections with increased greenhouse gas concentrations (using the mid-range IPCC A1B emissions scenario) with those under a mitigation scenario with large reductions in emissions (the E1 scenario). At the end of the twenty-first century, the global mean steric sea level rise is reduced by about a third in the mitigation scenario compared with the A1B scenario. Changes in surface air temperature are found to be poorly correlated with steric sea level changes. While the projected decreases in sea ice extent during the first half of the twenty-first century are independent of the season or scenario, especially in the Arctic, the seasonal cycle of sea ice extent is amplified. By the end of the century the Arctic becomes sea ice free in September in the A1B scenario in most models. In the mitigation scenario the ice does not disappear in the majority of models, but is reduced by 42 % of the present September extent. Results for Antarctic sea ice changes reveal large initial biases in the models and a significant correlation between projected changes and the initial extent. This latter result highlights the necessity for further refinements in Antarctic sea ice modelling for more reliable projections of future sea ice.

  7. Addressing language barriers to healthcare in India.

    PubMed

    Narayan, Lalit

    2013-01-01

    In spite of a growing recognition of the importance of doctor-patient communication, the issue of language barriers to healthcare has received very little attention in India. The Indian population speaks over 22 major languages with English used as the lingua franca for biomedicine. Large-scale internal migration has meant that health workers are encountering increasing instances of language discordance within clinical settings. Research done predominantly in the West has shown language discordance to significantly affect access to care, cause problems of comprehension and adherence, and decrease the satisfaction and quality of care. Addressing language barriers to healthcare in India requires a stronger political commitment to providing non-discriminatory health services, especially to vulnerable groups such as illiterate migrant workers. Research will have to address three broad areas: the ways in which language barriers affect health and healthcare, the efficacy of interventions to overcome language barriers, and the costs of language barriers and efforts to overcome them. There is a need to address such barriers in health worker education and clinical practice. Proven strategies such as hiring multilingual healthcare workers, providing language training to health providers, employing in situ translators or using telephone interpretation services will have to be evaluated for their appropriateness to the Indian context. Internet-based initiatives, the proliferation of mobile phones and recent advances in machine translation promise to contribute to the solution.

  8. Learn to Avoid or Overcome Leadership Obstacles

    ERIC Educational Resources Information Center

    D'Auria, John

    2015-01-01

    Leadership is increasingly recognized as an important factor in moving schools forward, yet we have been relatively random in how we prepare and support them. Four obstacles often block or diminish their effectiveness. Avoiding or overcoming each of these requires an underlying set of skills and knowledge that we believe can be learned and…

  9. Students Write to Overcome Learning Blocks.

    ERIC Educational Resources Information Center

    Lavoie, Dan; Backus, Ann

    1990-01-01

    Discussed is the use of writing as a tool to monitor student growth and development. The value of writing to help overcome obstacles such as misconceptions and preconceptions is stressed. A concept map of a hierarchy of writing strategies is provided. Stressed is the value of writing in the development of process skills. (CW)

  10. First Davis Strait discovery overcomes offshore hazards

    SciTech Connect

    Munro, R.G.

    1982-04-01

    In spite of icebergs umpredictable currents and brief drilling seasons, the first discovery well was completed recently in the Davis Strait. The success of this well, known as Hekja 0-71, has opened the waters off the northeastern coast of Canada to more exploration. A discussion is presented of how the well was drilled, the problems encountered and how they were overcome.

  11. Successful Writing: Five Roadblocks to Overcome

    ERIC Educational Resources Information Center

    King, Kathleen P.

    2013-01-01

    This article provides essential strategies to be more successful in one of the major roles in academia: writing. Most academics struggle with roadblocks in their writing process. We are forever battling to complete research articles, manuscripts, grant proposals or other documents. The strategies and perspective shared here help overcome several…

  12. Overcoming the Limitations of Learning Objects

    ERIC Educational Resources Information Center

    Wiley, David; Waters, Sandie; Dawson, Deonne; Lambert, Brent; Barclay, Matthew; Wade, David; Nelson, Laurie

    2004-01-01

    There are a number of issues that face individuals who would use learning objects for instructional purposes. These issues include problems with decontextualization, enabling meaningful reusability, and overcoming biases toward didactic approaches in the use of learning objects. We discuss these problems in some detail, and present a project-based…

  13. Evaluating Depth-Integrated Steric Contributions to Sea-Level Trends and Variability in Earth System Model Ensembles

    NASA Astrophysics Data System (ADS)

    Hogan, E.; Sriver, R. L.

    2015-12-01

    Earth system model ensembles exhibit considerable uncertainties surrounding trends and magnitude of steric sea-level variations, due in part to structural model differences, internal model variability, and parameterizations that influence ocean heat uptake. Here we analyze depth-integrated steric sea-level changes using the CMIP5 models and a new CESM ensemble that samples internal variability of the coupled Earth system. The CESM ensemble contains 50 members, with historical and future projections (1850-2100) initialized from unique model states sampled from a ~10,000 year fully coupled unforced equilibrium simulation. The CESM ensemble enables us to examine how initial conditions uncertainty (internal variability) within the full-ocean can influence depth-integrated steric sea-level variability. The second ensemble is comprised of runs from 32 different CMIP5 models. We performed grid-level drift correction for each model using the pre-industrial control simulations, which enables us to examine depth-integrated variability and trends due to different model structures. We compare and contrast our results with published observational datasets, and we analyze the effect of different sources of uncertainty on simulated sea-level variability and trends for different ocean depths. Results point to the importance of the deep ocean in attempting to attribute and predict temporal patterns of steric sea-level on a global scale.

  14. A sterically demanding organo-superbase avoids decomposition of a naked trifluoromethyl carbanion directly generated from fluoroform.

    PubMed

    Kawai, Hiroyuki; Yuan, Zhe; Tokunaga, Etsuko; Shibata, Norio

    2013-03-01

    A simple strategy avoiding the decomposition of a naked trifluoromethyl anion to difluorocarbene by a sterically very demanding organo-superbase without the help of a trifluoromethyl anion reservoir such as DMF is reported. The direct non-metallic trifluoromethylation of carbonyl compounds using fluoroform in the presence of t-Bu-P4 base afforded trifluoromethyl alcohols in high yields. PMID:23344691

  15. Comment on "Rabbit-Ears Hybrids, VSEPR Sterics, and Other Orbital Anachronisms": A Reply to a Criticism

    ERIC Educational Resources Information Center

    Hiberty, Philippe C.; Danovich, David; Shaik, Sason

    2015-01-01

    This commentary summarizes the authors' basic disagreements with the paper, "Rabbit-Ears, VSEPR Sterics, and Other Orbital Anachronisms," which criticizes the authors' usage of the hybrid orbitals for H[subscript 2]O in their book, "A Chemist's Guide to Valence Bond Theory" (Shaik and Hiberty, 2008). The current article shows…

  16. A sterically demanding organo-superbase avoids decomposition of a naked trifluoromethyl carbanion directly generated from fluoroform.

    PubMed

    Kawai, Hiroyuki; Yuan, Zhe; Tokunaga, Etsuko; Shibata, Norio

    2013-03-01

    A simple strategy avoiding the decomposition of a naked trifluoromethyl anion to difluorocarbene by a sterically very demanding organo-superbase without the help of a trifluoromethyl anion reservoir such as DMF is reported. The direct non-metallic trifluoromethylation of carbonyl compounds using fluoroform in the presence of t-Bu-P4 base afforded trifluoromethyl alcohols in high yields.

  17. Role of nanotechnology in HIV/AIDS treatment: potential to overcome the viral reservoir challenge.

    PubMed

    Amiji, Mansoor M; Vyas, Tushar K; Shah, Lipa K

    2006-08-01

    Insufficient concentrations and very short residence time of the anti-retroviral agents at the cellular and anatomical sites are among major factors that contribute to the failure of eradicating HIV from reservoirs and the development of multidrug resistance against antiretroviral agents. In recent years, nanotechnology-based drug delivery systems have shown remarkable ability to overcome many of the same anatomical and physiological barriers and deliver the therapeutic agents locally at the site of systemic diseases such as cancer.

  18. Comparative pharmacokinetics, distributions in tissue, and interactions with blood proteins of conventional and sterically stabilized liposomes containing 2',3'-dideoxyinosine.

    PubMed Central

    Harvie, P; Désormeaux, A; Bergeron, M C; Tremblay, M; Beauchamp, D; Poulin, L; Bergeron, M G

    1996-01-01

    The pharmacokinetics and distribution in tissue of 2',3'-dideoxyinosine (ddI) encapsulated in sterically stabilized liposomes have been evaluated in rats. Most of the sterically stabilized liposomes concentrated in the spleen with a peak level at 24 h after their intravenous injection. An extended half-life in plasma was observed for sterically stabilized liposomes (14.5 h) compared with that of conventional liposomes (3.9 h). The systemic clearance of ddI incorporated in sterically stabilized liposomes was 180 times lower than that of the free drug. The levels of in vitro and in vivo protein binding on both conventional and sterically stabilized liposomes were also evaluated. Results suggest that the amount of proteins associated with liposomes might not be the only factor involved in the in vivo clearance of liposomes, as this process may also be influenced by the nature of the bound blood proteins. PMID:8787911

  19. Unusually efficient pyridine photodissociation from Ru(II) complexes with sterically bulky bidentate ancillary ligands.

    PubMed

    Knoll, Jessica D; Albani, Bryan A; Durr, Christopher B; Turro, Claudia

    2014-11-13

    The introduction of steric bulk to the bidentate ligand in [Ru(tpy)(bpy)(py)](2+) (1; tpy = 2,2':2',6″-terpyridine; bpy = 2,2'-bipyridine; py = pyridine) to provide [Ru(tpy)(Me2bpy)(py)](2+) (2; Me2bpy = 6,6'-dimethyl-2,2'-bipyridine) and [Ru(tpy)(biq)(py)](2+) (3; biq = 2,2'-biquinoline) facilitates photoinduced dissociation of pyridine with visible light. Upon irradiation of 2 and 3 in CH3CN (λirr = 500 nm), ligand exchange occurs to produce the corresponding [Ru(tpy)(NN)(NCCH3)](2+) (NN = Me2bpy, biq) complex with quantum yields, Φ500, of 0.16(1) and 0.033(1) for 2 and 3, respectively. These values represent an increase in efficiency of the reaction by 2-3 orders of magnitude as compared to that of 1, Φ500 < 0.0001, under similar experimental conditions. The photolysis of 2 and 3 in H2O with low energy light to produce [Ru(tpy)(NN)(OH2)](2+) (NN = Me2bpy, biq) also proceeds rapidly (λirr > 590 nm). Complexes 1-3 are stable in the dark in both CH3CN and H2O under similar experimental conditions. X-ray crystal structures and theoretical calculations highlight significant distortion of the planes of the bidentate ligands in 2 and 3 relative to that of 1. The crystallographic dihedral angles defined by the bidentate ligand, Me2bpy in 2 and biq in 3, and the tpy ligand were determined to be 67.87° and 61.89°, respectively, whereas only a small distortion from the octahedral geometry is observed between bpy and tpy in 1, 83.34°. The steric bulk afforded by Me2bpy and biq also result in major distortions of the pyridine ligand in 2 and 3, respectively, relative to 1, which are believed to weaken its σ-bonding and π-back-bonding to the metal and play a crucial role in the efficiency of the photoinduced ligand exchange. The ability of 2 and 3 to undergo ligand exchange with λirr > 590 nm makes them potential candidates to build photochemotherapeutic agents for the delivery of drugs with pyridine binding groups.

  20. Unusually Efficient Pyridine Photodissociation from Ru(II) Complexes with Sterically Bulky Bidentate Ancillary Ligands

    PubMed Central

    2015-01-01

    The introduction of steric bulk to the bidentate ligand in [Ru(tpy)(bpy)(py)]2+ (1; tpy = 2,2′:2′,6″-terpyridine; bpy = 2,2′-bipyridine; py = pyridine) to provide [Ru(tpy)(Me2bpy)(py)]2+ (2; Me2bpy = 6,6′-dimethyl-2,2′-bipyridine) and [Ru(tpy)(biq)(py)]2+ (3; biq = 2,2′-biquinoline) facilitates photoinduced dissociation of pyridine with visible light. Upon irradiation of 2 and 3 in CH3CN (λirr = 500 nm), ligand exchange occurs to produce the corresponding [Ru(tpy)(NN)(NCCH3)]2+ (NN = Me2bpy, biq) complex with quantum yields, Φ500, of 0.16(1) and 0.033(1) for 2 and 3, respectively. These values represent an increase in efficiency of the reaction by 2–3 orders of magnitude as compared to that of 1, Φ500 < 0.0001, under similar experimental conditions. The photolysis of 2 and 3 in H2O with low energy light to produce [Ru(tpy)(NN)(OH2)]2+ (NN = Me2bpy, biq) also proceeds rapidly (λirr > 590 nm). Complexes 1–3 are stable in the dark in both CH3CN and H2O under similar experimental conditions. X-ray crystal structures and theoretical calculations highlight significant distortion of the planes of the bidentate ligands in 2 and 3 relative to that of 1. The crystallographic dihedral angles defined by the bidentate ligand, Me2bpy in 2 and biq in 3, and the tpy ligand were determined to be 67.87° and 61.89°, respectively, whereas only a small distortion from the octahedral geometry is observed between bpy and tpy in 1, 83.34°. The steric bulk afforded by Me2bpy and biq also result in major distortions of the pyridine ligand in 2 and 3, respectively, relative to 1, which are believed to weaken its σ-bonding and π-back-bonding to the metal and play a crucial role in the efficiency of the photoinduced ligand exchange. The ability of 2 and 3 to undergo ligand exchange with λirr > 590 nm makes them potential candidates to build photochemotherapeutic agents for the delivery of drugs with pyridine binding groups. PMID:25027458

  1. Unlocking the steric gate of DNA polymerase η leads to increased genomic instability in Saccharomyces cerevisiae

    PubMed Central

    Donigan, Katherine A.; Cerritelli, Susana M.; McDonald, John P.; Vaisman, Alexandra; Crouch, Robert J.; Woodgate, Roger

    2015-01-01

    DNA polymerase η (pol η) is best characterized for its ability to perform accurate and efficient translesion DNA synthesis (TLS) through cyclobutane pyrimidine dimers (CPDs). To ensure accurate bypass the polymerase is not only required to select the correct base, but also discriminate between NTPs and dNTPs. Most DNA polymerases have a conserved “steric gate” residue which functions to prevent incorporation of NMPs during DNA synthesis. Here, we demonstrate that the Phe35 residue of S. cerevisiae pol η functions as a steric gate to limit the use of ribonucleotides during polymerization both in vitro and in vivo. Unlike the related polι enzyme, wild-type pol η does not readily incorporate NMPs in vitro. In contrast, a pol η F35A mutant incorporates NMPs on both damaged and undamaged DNA in vitro with a high degree of base selectivity. An S. cerevisiae strain expressing pol η F35A (rad30-F35A) that is also deficient for nucleotide excision repair (rad1Δ) and the TLS polymerase, pol ζ (rev3Δ), is extremely sensitive to UV-light. The sensitivity is due, in part, to RNaseH2 activity, as an isogenic rnh201Δ strain is roughly 50-fold more UV-resistant than its RNH201+ counterpart. Interestingly the rad1Δ rev3Δ rad30-F35A rnh201Δ strain exhibits a significant increase in the extent of spontaneous mutagenesis with a spectrum dominated by 1 bp deletions at runs of template Ts. We hypothesize that the increased mutagenesis is due to rA incorporation at these sites and that the short poly rA tract is subsequently repaired in an error-prone manner by a novel repair pathway that is specifically targeted to polyribonucleotide tracks. These data indicate that under certain conditions, pol η can compete with the cell’s replicases and gain access to undamaged genomic DNA. Such observations are consistent with a role for pol η in replicating common fragile sites (CFS) in human cells. PMID:26340535

  2. Immunobiological barriers to xenotransplantation.

    PubMed

    Cooper, David K C; Ekser, Burcin; Tector, A Joseph

    2015-11-01

    Binding of natural anti-pig antibodies in humans and nonhuman primates to carbohydrate antigens expressed on the transplanted pig organ, the most important of which is galactose-α1,3-galactose (Gal), activate the complement cascade, which results in destruction of the graft within minutes or hours, known as hyperacute rejection. Even if antibody is removed from the recipient's blood by plasmapheresis, recovery of antibody is associated with acute humoral xenograft rejection. If immunosuppressive therapy is inadequate, the development of high levels of T cell-dependent elicited anti-pig IgG similarly results in graft destruction, though classical acute cellular rejection is rarely seen. Vascular endothelial activation by low levels of anti-nonGal antibody, coupled with dysregulation of the coagulation-anticoagulation systems between pigs and primates, leads to a thrombotic microangiopathy in the graft that may be associated with a consumptive coagulopathy in the recipient. The most successful approach to overcoming these barriers is by genetically-engineering the pig to provide it with resistance to the human humoral and cellular immune responses and to correct the coagulation discrepancies between the two species. Organs and cells from pigs that (i) do not express the important Gal antigen, (ii) express a human complement-regulatory protein, and (iii) express a human coagulation-regulatory protein, when combined with an effective immunosuppressive regimen, have been associated with prolonged pig graft survival in nonhuman primates.

  3. Barriers to accessing surgical care in Pakistan: healthcare barrier model and quantitative systematic review.

    PubMed

    Irfan, Furqan B; Irfan, Bismah B; Spiegel, David A

    2012-07-01

    Inadequate access to surgical services results in increased morbidity and mortality from a spectrum of conditions in Pakistan. We employed a modification of Andersen's model of health services utilization and developed a 'Healthcare Barrier Model,' to characterize the barriers to accessing health care in developing countries, using surgical care in Pakistan as a case study. We performed a literature search from MEDLINE, EMBASE, CINAHL, SCOPUS, Global Health Database, and Cochrane Central Register of Controlled Trials, and selected 64 of 3113 references for analysis. Patient-related variables included age (elderly), gender (female), preferential use of alternative health providers (Hakeem, traditional healers, others), personal perceptions regarding disease and potential for treatment, poverty, personal expenses for healthcare, lack of social support, geographic constraints to accessing a health facility, and compromised general health status as it relates to the development of surgical disease. Environmental barriers include deficiencies in governance, the burden of displaced or refugee populations, and aspects of the medicolegal system, which impact treatment and referral. Barriers relating to the health system include deficiencies in capacity (infrastructure, physical resources, human resources) and organization, and inadequate monitoring. Provider-related barriers include deficiencies in knowledge and skills (and ongoing educational opportunities), delays in referral, deficient communication, and deficient numbers of female health providers for female patients. The Healthcare Barrier model addresses this broad spectrum of barriers and is designed to help formulate a framework of healthcare barriers. To overcome these barriers will require a multidisciplinary, multisectoral effort aimed at strengthening the health system. PMID:22079839

  4. Sprache als Barriere (Language as a Barrier)

    ERIC Educational Resources Information Center

    Mattheier, Klaus

    1974-01-01

    The concept of language barrier has its derivations in the fields of dialectology, sociology and psychology. In contemporary usage however, the concept has two meanings i.e. regional-cultural barrier and socio-cultural barrier. (Text is in German.) (DS)

  5. Glycoprotein mucin molecular brush on cancer cell surface acting as mechanical barrier against drug delivery

    NASA Astrophysics Data System (ADS)

    Wang, Xin; Shah, Aalok A.; Campbell, Robert B.; Wan, Kai-tak

    2010-12-01

    Uptake of cytotoxic drugs by typical tumor cells is limited by the dense dendritic network of oligosaccharide mucin chains that forms a mechanical barrier. Atomic force microscopy is used to directly measure the force needed to pierce the mucin layer to reach the cell surface. Measurements are analyzed by de Gennes' steric reptation theory. Multidrug resistant ovarian tumor cells shows significantly larger penetration load compared to the wide type. A pool of pancreatic, lung, colorectal, and breast cells are also characterized. The chemotherapeutic agent, benzyl-α-GalNac, for inhibiting glycosylation is shown to be effective in reducing the mechanical barrier.

  6. Rectification of swimming bacteria and self-driven particle systems by arrays of asymmetric barriers.

    PubMed

    Wan, M B; Olson Reichhardt, C J; Nussinov, Z; Reichhardt, C

    2008-07-01

    We show that the recent experimental observation of the rectification of swimming bacteria in a system with an array of asymmetric barriers occurs due to the ballistic component of the bacteria trajectories introduced by the bacterial "motor." Each bacterium selects a random direction for motion and then moves in this direction for a fixed period of time before randomly changing its orientation and moving in a new direction. In the limit where the bacteria undergo only Brownian motion on the size scale of the barriers, rectification does not occur. We examine the effects of steric interactions between the bacteria and observe a clogging effect upon increasing the bacteria density. PMID:18764155

  7. Steric hindrance and the enhanced stability of light rare-earth elements in hydrothermal fluids

    USGS Publications Warehouse

    Mayanovic, Robert A.; Anderson, Alan J.; Bassett, William A.; Chou, I.-Ming

    2009-01-01

    A series of X-ray absorption spectroscopy (XAS) experiments were made to determine the structure and stability of aqueous REE (La, Nd, Gd, and Yb) chloride complexes to 500 ??C and 520 MPa. The REE3+ ions exhibit inner-sphere chloroaqua complexation with a steady increase of chloride coordination with increasing temperature in the 150 to 500 ??C range. Furthermore, the degree of chloride coordination of REE3+ inner-sphere chloroaqua complexes decreases significantly from light to heavy REE. These results indicate that steric hindrance drives the reduction of chloride coordination of REE3+ inner-sphere chloroaqua complexes from light to heavy REE. This results in greater stability and preferential transport of light REE3+ over heavy REE3+ ions in saline hydrothermal fluids. Accordingly, the preferential mobility of light REE directly influences the relative abundance of REE in rocks and minerals and thus needs to be considered in geochemical modeling of petrogenetic and ore-forming processes affected by chloride-bearing hydrothermal fluids.

  8. Effect of fullerene on the dispersibility of nanostructured lipid particles and encapsulation in sterically stabilized emulsions.

    PubMed

    Kulkarni, Chandrashekhar V; Moinuddin, Zeinab; Agarwal, Yash

    2016-10-15

    We report on the effect of fullerenes (C60) on the stability of nanostructured lipid emulsions. These (oil-in-water) emulsions are essentially aqueous dispersions of lipid particles exhibiting self-assembled nanostructures at their cores. The majority of previous studies on fullerenes were focused on planar and spherical lipid bilayer systems including pure lipids and liposomes. In this work, fullerenes were interacted with a lipid that forms nanostructured dispersions of non-lamellar self-assemblies. A range of parameters including the composition of emulsions and sonication parameters were examined to determine the influence of fullerenes on in-situ and pre-stabilized lipid emulsions. We found that fullerenes mutually stabilize very low concentrations of lipid molecules, while other concentration emulsions struggle to stay stable or even to form at first instance; we provide hypotheses to support these observations. Interestingly though, we were able to encapsulate varying amounts of fullerenes in sterically stabilized emulsions. This step has a significant positive impact, as we could effectively control an inherent aggregation tendency of fullerenes in aqueous environments. These novel hybrid nanomaterials may open a range of avenues for biotechnological and biomedical applications exploiting properties of both lipid and fullerene nanostructures.

  9. A sterically congested cis-stilbene and its phosphonium salt precursor.

    PubMed

    Shivaprakash, Shivanna; Reddy, G Chandrasekara; Jasinski, Jerry P; Millikan, Sean P; Duff, Courtney E; Glidewell, Christopher

    2015-06-01

    Triphenyl(2,4,5-trimethoxybenzyl)phosphonium chloride is formed in solvent-free form by the reaction under anhydrous conditions between triphenylphosphane and 2,4,5-trimethoxybenzyl chloride, but when it is crystallized from a mixture of ethyl acetate and chloroform in the presence of air it forms a stoichiometric monohydrate, C28H28O3P(+)·Cl(-)·H2O, (I). The reactions between the anhydrous phosphonium salt and alkoxy-substituted benzaldehydes, using Wittig reactions in the presence of potassium tert-butoxide, provide a series of multiply substituted stilbenes, most of which were assigned the Z configuration on the basis of their NMR spectra. However, no such deduction could be made for the symmetrically substituted (Z)-2,2',4,4',5,5'-hexamethoxystilbene, C20H24O6, (II). Compound (II) does in fact have the Z configuration and the molecular geometry provides evidence for steric congestion around the central double bond; in particular, the central alkene fragment is nonplanar, with a C-C=C-C torsion angle of 7.8 (4)°. In hydrated salt (I), the chloride anions and water molecules are linked by O-H···Cl hydrogen bonds to form C2(1)(4) chains; each cation is linked by C-H···O hydrogen bonds to two different chains, so forming a sheet structure. There are no direction-specific intermolecular interactions in the structure of (II).

  10. Sterically stabilized superparamagnetic liposomes for MR imaging and cancer therapy: pharmacokinetics and biodistribution.

    PubMed

    Plassat, V; Martina, M S; Barratt, G; Ménager, C; Lesieur, S

    2007-11-01

    Pharmacokinetics of magnetic-fluid-loaded liposomes (MFLs) with mean hydrodynamic diameter of 200 nm sterically stabilized by poly(ethylene glycol) (PEG) and labelled by a fluorescent lipid probe, N-(lissamine rhodamine B sulfonyl) phosphatidylethanolamine (Rho-PE) was studied. The loading consisted in an aqueous suspension of maghemite nanocrystals close to 8 nm in size at 1.7 Fe(III)mol/mol total lipids ratio. Double tracking of MFL in blood was performed versus time after intravenous administration in mice. Lipids constituting vesicle membrane were followed by Rho-PE fluorescence spectroscopy while iron oxide was determined independently by relaxometry. MFLs circulating in the vascular compartment conserved their vesicle structure and content. The pharmacokinetic profile was characterized by two first-order kinetics of elimination with distinct plasmatic half-lives of 70 min and 12.5 h. Iron biodistribution and organ histology clearly highlighted preferential MFL accumulation within liver and spleen. The pathway in spleen supported that elimination was governed by the mononuclear phagocyte system (MPS). PEG coating was essential to prolong MFL circulation time whereas iron oxide loading tends to favour uptake by the MPS. Despite partial uptake in the earlier times after administration, MFLs exhibited long circulation behaviour over a 24-h period that, coupled to magnetic targeting, encourages further use in drug delivery. PMID:17583452

  11. The interaction of sterically stabilized magnetic nanoparticles with fresh human red blood cells

    PubMed Central

    Pham, Binh TT; Jain, Nirmesh; Kuchel, Philip W; Chapman, Bogdan E; Bickley, Stephanie A; Jones, Stephen K; Hawkett, Brian S

    2015-01-01

    Sterically stabilized superparamagnetic iron oxide nanoparticles (SPIONs) were incubated with fresh human erythrocytes (red blood cells [RBCs]) to explore their potential application as magnetic resonance imaging contrast agents. The chemical shift and linewidth of 133Cs+ resonances from inside and outside the RBCs in 133Cs nuclear magnetic resonance spectra were monitored as a function of time. Thus, we investigated whether SPIONs of two different core sizes and with three different types of polymeric stabilizers entered metabolically active RBCs, consuming glucose at 37°C. The SPIONs broadened the extracellular 133Cs+ nuclear magnetic resonance, and brought about a small change in its chemical shift to a higher frequency; while the intracellular resonance remained unchanged in both amplitude and chemical shift. This situation pertained over incubation times of up to 90 minutes. If the SPIONs had entered the RBCs, the intracellular resonance would have become broader and possibly even shifted. Therefore, we concluded that our SPIONs did not enter the RBCs. In addition, the T2 relaxivity of the small and large particles was 368 and 953 mM−1 s−1, respectively (three and nine times that of the most effective commercially available samples). This suggests that these new SPIONs will provide a superior performance to any others reported thus far as magnetic resonance imaging contrast agents. PMID:26604741

  12. An investigation of some sterically hindered amines as potential carbon dioxide scrubbing compounds

    SciTech Connect

    Hook, R.J.

    1997-05-01

    In order to improve the efficiency of the carbon dioxide cycling process and to reduce amine emissions, a series of nonvolatile amino acid salts with sterically hindered amine groups were investigated to determine their potential as direct replacements for monoethanolamine (MEA) in submarine-based CO{sub 2} scrubbers. Absorption from atmospheres containing various levels of CO{sub 2} was measured to assess the total capacities and absorption rates of amine solutions. The regeneration rates and extent of CO{sub 2} desorption were established by heating these solutions. {sup 13}C NMR spectroscopy was used to establish reaction products and solution compositions after both absorption and desorption. Methyl groups substituted adjacent to the amine were found to increase solution absorption capacities but with an overall reduction in absorption rate. Poor absorption rates at low CO{sub 2} levels and precipitation problems would prevent the {alpha}-dimethylamines examined from being used in existing submarine scrubbers. These amines, however, show potential as replacements in industrial CO{sub 2} scrubbing processes.

  13. Pluronic® coated sterically stabilized magnetite nanoparticles for hyperthermia applications

    NASA Astrophysics Data System (ADS)

    Rodrigues, E. C.; Morales, M. A.; de Medeiros, S. N.; Suguihiro, N. M.; Baggio-Saitovitch, E. M.

    2016-10-01

    We report the synthesis of magnetite nanoparticles by ball milling of α-Fe in water and its functionalization with oleic acid and Pluronic® F127 for use in hyperthermia applications. The samples were characterized by transmission electron microscopy, DC magnetometry, X-ray diffraction, infrared spectroscopy and heat release studies under an AC magnetic field. The magnetite phase corresponded to 96 wt% and there was a small contribution of 4 wt% of α-Fe. The magnetite particles have a main size of 22 nm and oleic acid layer thickness of 1.9 nm. Magnetic measurements indicate the particles are blocked at 300 K and exhibit the Verwey transition at 119 K. At 5 K the saturation magnetization obtained from the law of approach to saturation was of 95 emu/g. In the heat release studies, the sterically stabilized particles have a temperature increase, ΔT, of 43 °C in 350 s. The Pluronic® coated particles, dispersed in water at 50 mg/ml, exhibited a ΔT=10.5 °C in 350 s, and this value remained nearly constant for periods of up to 650 s. The specific absorption rate (SAR) was of 6.4 W/g indicating that this sample may be used for the lyse of tumor cells.

  14. Effect of fullerene on the dispersibility of nanostructured lipid particles and encapsulation in sterically stabilized emulsions.

    PubMed

    Kulkarni, Chandrashekhar V; Moinuddin, Zeinab; Agarwal, Yash

    2016-10-15

    We report on the effect of fullerenes (C60) on the stability of nanostructured lipid emulsions. These (oil-in-water) emulsions are essentially aqueous dispersions of lipid particles exhibiting self-assembled nanostructures at their cores. The majority of previous studies on fullerenes were focused on planar and spherical lipid bilayer systems including pure lipids and liposomes. In this work, fullerenes were interacted with a lipid that forms nanostructured dispersions of non-lamellar self-assemblies. A range of parameters including the composition of emulsions and sonication parameters were examined to determine the influence of fullerenes on in-situ and pre-stabilized lipid emulsions. We found that fullerenes mutually stabilize very low concentrations of lipid molecules, while other concentration emulsions struggle to stay stable or even to form at first instance; we provide hypotheses to support these observations. Interestingly though, we were able to encapsulate varying amounts of fullerenes in sterically stabilized emulsions. This step has a significant positive impact, as we could effectively control an inherent aggregation tendency of fullerenes in aqueous environments. These novel hybrid nanomaterials may open a range of avenues for biotechnological and biomedical applications exploiting properties of both lipid and fullerene nanostructures. PMID:27416287

  15. Grafting zwitterionic polymer onto cryogel surface enhances protein retention in steric exclusion chromatography on cryogel monolith.

    PubMed

    Tao, Shi-Peng; Zheng, Jie; Sun, Yan

    2015-04-10

    Cryogel monoliths with interconnected macropores (10-100μm) and hydrophilic surfaces can be employed as chromatography media for protein retention in steric exclusion chromatography (SXC). SXC is based on the principle that the exclusion of polyethylene glycol (PEG) on both a hydrophilic chromatography surface and a protein favors their association, leading to the protein retention on the chromatography surface. Elution of the retained protein can be achieved by reducing PEG concentration. In this work, the surface of polyacrylamide-based cryogel monolith was modified by grafting zwitterionic poly(carboxybetaine methacrylate) (pCBMA), leading the increase in the surface hydrophilicity. Observation by scanning electron microscopy revealed the presence of the grafted pCBMA chain clusters on the cryogel surface, but pCBMA grafting did not result in the changes of the physical properties of the monolith column, and the columns maintained good recyclability in SXC. The effect of the surface grafting on the SXC behavior of γ-globulin was investigated in a wide flow rate range (0.6-12cm/min). It was found that the dynamic retention capacity increased 1.4-1.8 times by the zwitterionic polymer grafting in the flow rate range of 1.5-12cm/min. The mechanism of enhanced protein retention on the zwitterionic polymer-grafted surface was proposed. The research proved that zwitterionic polymer modification was promising for the development of new materials for SXC applications.

  16. On the role of steric clashes in methylation control of restriction endonuclease activity

    PubMed Central

    Mierzejewska, Karolina; Bochtler, Matthias; Czapinska, Honorata

    2016-01-01

    Restriction-modification systems digest non-methylated invading DNA, while protecting host DNA against the endonuclease activity by methylation. It is widely believed that the methylated DNA would not ‘fit’ into the binding site of the endonuclease in the productive orientation, and thus steric clashes should account for most of the protection. We test this concept statistically by grafting methyl groups in silico onto non-methylated DNA in co-crystal structures with restriction endonucleases. Clash scores are significantly higher for protective than non-protective methylation (P < 0.05% according to the Wilcoxon rank sum test). Structural data alone are sufficient to distinguish between protective and non-protective DNA methylation with 90% confidence and decision thresholds of 1.1 Å and 48 Å3 for the most severe distance-based and cumulative volume-based clash with the protein, respectively (0.1 Å was deducted from each interatomic distance to allow for coordinate errors). The most severe clashes are more pronounced for protective methyl groups attached to the nitrogen atoms (N6-methyladenines and N4-methylcytosines) than for C5-methyl groups on cytosines. Cumulative clashes are comparable for all three types of protective methylation. PMID:26635397

  17. The interaction of sterically stabilized magnetic nanoparticles with fresh human red blood cells.

    PubMed

    Pham, Binh T T; Jain, Nirmesh; Kuchel, Philip W; Chapman, Bogdan E; Bickley, Stephanie A; Jones, Stephen K; Hawkett, Brian S

    2015-01-01

    Sterically stabilized superparamagnetic iron oxide nanoparticles (SPIONs) were incubated with fresh human erythrocytes (red blood cells [RBCs]) to explore their potential application as magnetic resonance imaging contrast agents. The chemical shift and linewidth of (133)Cs(+) resonances from inside and outside the RBCs in (133)Cs nuclear magnetic resonance spectra were monitored as a function of time. Thus, we investigated whether SPIONs of two different core sizes and with three different types of polymeric stabilizers entered metabolically active RBCs, consuming glucose at 37°C. The SPIONs broadened the extracellular (133)Cs(+) nuclear magnetic resonance, and brought about a small change in its chemical shift to a higher frequency; while the intracellular resonance remained unchanged in both amplitude and chemical shift. This situation pertained over incubation times of up to 90 minutes. If the SPIONs had entered the RBCs, the intracellular resonance would have become broader and possibly even shifted. Therefore, we concluded that our SPIONs did not enter the RBCs. In addition, the T 2 relaxivity of the small and large particles was 368 and 953 mM(-1) s(-1), respectively (three and nine times that of the most effective commercially available samples). This suggests that these new SPIONs will provide a superior performance to any others reported thus far as magnetic resonance imaging contrast agents. PMID:26604741

  18. A monofunctional trinuclear platinum complex with steric hindrance demonstrates strong cytotoxicity against tumor cells.

    PubMed

    Wu, Shangnong; Wang, Xiaoyong; He, Yafeng; Zhu, Zhenzhu; Zhu, Chengcheng; Guo, Zijian

    2014-10-01

    Polynuclear platinum complexes constitute a special class of hopeful antitumor agents. In this study, a Y-type monofunctional trinuclear platinum complex (MTPC) with 1,3,5-tris(pyridin-2-ylmethoxy)benzene, ammine and chloride as ligands was synthesized and characterized by (1)H NMR and electrospray ionization mass spectrometry (ESI-MS). The DNA binding mode of MTPC was investigated using circular dichroism spectroscopy and gel electrophoresis, and the reactivity of MTPC towards glutathione was studied by (1)H NMR and ESI-MS. The results show that MTPC can affect the conformation of calf-thymus DNA (CT-DNA) significantly and tends to form 1,4-GG rather than 1,2-GG intrastrand crosslinks, which are different from the instance of cisplatin. MTPC reacts with glutathione quite slowly in comparison with cisplatin because of the steric hindrance. The cytotoxicity of MTPC was tested on the human breast cancer cell line MCF-7, the human non-small-cell lung cancer cell line A549, and the human ovarian cancer cell line Skov-3 by the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. MTPC is more potent than or comparable to cisplatin. The cellular inhibition mode of MTPC was examined by flow cytometry using MCF-7 cells. MTPC arrests the cell cycle mainly in G2 or M phase, while cisplatin arrests the cell cycle in S phase. Similar to cisplatin, MTPC kills the cells predominantly through an apoptotic pathway.

  19. Reorientation of Isomeric Butanols: The Multiple Effects of Steric Bulk Arrangement on Hydrogen-Bond Dynamics.

    PubMed

    Mesele, Oluwaseun O; Vartia, Anthony A; Laage, Damien; Thompson, Ward H

    2016-03-01

    Molecular dynamics simulations are used to investigate OH reorientation in the four isomeric butanols in their bulk liquid state to examine the influence of the arrangement of the steric bulk on the alcohol reorientational and hydrogen-bond (H-bond) dynamics. The results are interpreted within the extended jump model in which the OH reorientation is decomposed into contributions due to "jumps" between H-bond partners and "frame" reorientation of the intact H-bonded pair. Reorientation is fastest in iso-butanol and slowest in tert-butanol, while sec- and n-butanol have similar reorientation times. This latter result is a fortuitous cancellation between the jump and frame reorientation in the two alcohols. The extended jump model is shown to provide a quantitative description of the OH reorientation times. A detailed analysis of the jump times shows that a combination of entropic, enthalpic, and dynamical factors, including transition state recrossing effects, all play a role. A simple model based on the liquid structure is proposed to estimate the energetic and entropic contributions to the jump time. This represents the groundwork for a predictive model of OH reorientation in alcohols, but additional studies are required to better understand the frame reorientation and transition state recrossing effects.

  20. The controlled intravenous delivery of drugs using PEG-coated sterically stabilized nanospheres☆

    PubMed Central

    Gref, R.; Domb, A.; Quellec, P.; Blunk, T.; Müller, R.H.; Verbavatz, J.M.; Langer, R.

    2014-01-01

    Injectable blood persistent particulate carriers have important therapeutic application in site-specific drug delivery or medical imaging. However, injected particles are generally eliminated by the reticuloendothelial system within minutes after administration and accumulate in the liver and spleen. To obtain a coating that might prevent opsonization and subsequent recognition by the macrophages, sterically stabilized nanospheres were developed using amphiphilic diblock or multiblock copolymers. The nanospheres are composed of a hydrophilic polyethylene glycol coating and a biodegradable core in which various drugs were encapsulated. Hydrophobic drugs, such as lidocaine, were entrapped up to 45 wt% and the release kinetics were governed by the polymer physico-chemical characteristics. Plasma protein adsorption was drastically reduced on PEG-coated particles compared to non-coated ones. Relative protein amounts were time-dependent. The nanospheres exhibited increased blood circulation times and reduced liver accumulation, depending on the coating polyethylene glycol molecular weight and surface density. They could be freeze-dried and redispersed in aqueous solutions and possess good shelf stability. It may be possible to tailor “optimal” polymers for given therapeutic applications. PMID:25170183

  1. Grafting zwitterionic polymer onto cryogel surface enhances protein retention in steric exclusion chromatography on cryogel monolith.

    PubMed

    Tao, Shi-Peng; Zheng, Jie; Sun, Yan

    2015-04-10

    Cryogel monoliths with interconnected macropores (10-100μm) and hydrophilic surfaces can be employed as chromatography media for protein retention in steric exclusion chromatography (SXC). SXC is based on the principle that the exclusion of polyethylene glycol (PEG) on both a hydrophilic chromatography surface and a protein favors their association, leading to the protein retention on the chromatography surface. Elution of the retained protein can be achieved by reducing PEG concentration. In this work, the surface of polyacrylamide-based cryogel monolith was modified by grafting zwitterionic poly(carboxybetaine methacrylate) (pCBMA), leading the increase in the surface hydrophilicity. Observation by scanning electron microscopy revealed the presence of the grafted pCBMA chain clusters on the cryogel surface, but pCBMA grafting did not result in the changes of the physical properties of the monolith column, and the columns maintained good recyclability in SXC. The effect of the surface grafting on the SXC behavior of γ-globulin was investigated in a wide flow rate range (0.6-12cm/min). It was found that the dynamic retention capacity increased 1.4-1.8 times by the zwitterionic polymer grafting in the flow rate range of 1.5-12cm/min. The mechanism of enhanced protein retention on the zwitterionic polymer-grafted surface was proposed. The research proved that zwitterionic polymer modification was promising for the development of new materials for SXC applications. PMID:25757821

  2. Core-modified porphyrins. Part 4: Steric effects on photophysical and biological properties in vitro.

    PubMed

    You, Youngjae; Gibson, Scott L; Hilf, Russell; Ohulchanskyy, Tymish Y; Detty, Michael R

    2005-03-15

    21,23-Dithiaporphyrins (2-10) were designed and prepared as analogues of 5,20-diphenyl-10,15-bis(4-carboxylatomethoxy)phenyl-21,23-dithiaporphyrin (1) to examine the impact of steric bulk at the 5- and 20-meso positions as well as the impact of symmetry. Changes at the meso positions had minimal impact on the UV-vis-near-IR absorption spectra, quantum yields for the generation of singlet oxygen, and quantum yields for fluorescence and some impact on values of the octanol/water partition coefficient. Of the compounds 1-10, 5-phenyl-20-(2-thienyl)-10,15-bis-(4-carboxylatomethoxy-phenyl)-21,23-dithiaporphyrin (3) showed the greatest phototoxicity toward cultured R3230AC cells, with 68% cell kill at 1 x 10(-7)M and irradiation with 5J cm(-2) of 350-750 nm light. Results in this study suggest that smaller substituents on the meso ring and less symmetrical compounds are more effective as photosensitizers than compounds with two bulky substituents at adjoining meso sites and a higher symmetry. The mitochondria appear to be involved in the process of phototoxicity as determined by the inhibition of whole cell cytochrome c oxidase activity in cells treated with 3 and light. No impact upon mitochondrial cytochrome c oxidase activity was observed in cells treated with 3 and no light. Fluorescence microscopy studies suggest that the mitochondria are not initial sites of accumulation of 3.

  3. Antioxidant Properties of 2-Hydroxyethyl Methacrylate-Based Copolymers with Incorporated Sterically Hindered Amine.

    PubMed

    Poláková, L; Raus, V; Kostka, L; Braunová, A; Pilař, J; Lobaz, V; Pánek, J; Sedláková, Z

    2015-09-14

    A series of model linear copolymers of 2-hydroxyethyl methacrylate (HEMA) and a sterically hindered amine derivative [N-(2,2,6,6-tetramethyl-piperidin-4-yl)methacrylamide (HAS)] were synthesized and characterized. Scavenging activities of the copolymers against reactive oxygen species (peroxyl and hydroxyl radicals) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals were determined. It was found that copolymers with medium HAS content (3.5-4.0 mol %) were better scavengers than copolymers with lower and higher HAS content and also than polyHEMA and polyHAS homopolymers and the HAS monomer. Importantly, these copolymers compared favorably even to established low-molecular weight antioxidant standards (BHA and dexpanthenol). Monomer reactivity ratios were determined, and the microstructure of the copolymers was assessed. Subsequently, cross-linked copolymers in the powder and film forms with optimal HAS content were synthesized. Their scavenging activities against the three types of radicals were determined, revealing that these hydrogels are potent scavengers of reactive oxygen species. PMID:26258477

  4. Correlation of the solubility of several aromatics and terpenes in aqueous hydroxypropyl-beta-cyclodextrin with steric and hydrophobicity parameters.

    PubMed

    Demian, B A

    2000-10-01

    The solubility isotherms of nineteen aromatics and terpenes in aqueous hydroxypropyl-beta-cyclodextrin were determined to be straight lines. This is explained by the host-guest complexation which is characteristic for the whole class of cyclodextrins and derivatives. The slopes of the solubility isotherms correlate with Sterimol L and log P(ow) as descriptors of the steric fit and hydrophobicity match, in accord with the qualitative representation of the phenomenon.

  5. Correlation of the solubility of several aromatics and terpenes in aqueous hydroxypropyl-beta-cyclodextrin with steric and hydrophobicity parameters.

    PubMed

    Demian, B A

    2000-10-01

    The solubility isotherms of nineteen aromatics and terpenes in aqueous hydroxypropyl-beta-cyclodextrin were determined to be straight lines. This is explained by the host-guest complexation which is characteristic for the whole class of cyclodextrins and derivatives. The slopes of the solubility isotherms correlate with Sterimol L and log P(ow) as descriptors of the steric fit and hydrophobicity match, in accord with the qualitative representation of the phenomenon. PMID:11093722

  6. Strategies to Overcome Heparins’ Low Oral Bioavailability

    PubMed Central

    Neves, Ana Rita; Correia-da-Silva, Marta; Sousa, Emília; Pinto, Madalena

    2016-01-01

    Even after a century, heparin is still the most effective anticoagulant available with few side effects. The poor oral absorption of heparins triggered the search for strategies to achieve oral bioavailability since this route has evident advantages over parenteral administration. Several approaches emerged, such as conjugation of heparins with bile acids and lipids, formulation with penetration enhancers, and encapsulation of heparins in micro and nanoparticles. Some of these strategies appear to have potential as good delivery systems to overcome heparin’s low oral bioavailability. Nevertheless, none have reached the market yet. Overall, this review aims to provide insights regarding the oral bioavailability of heparin. PMID:27367704

  7. Overcoming Challenges in Engineering the Genetic Code.

    PubMed

    Lajoie, M J; Söll, D; Church, G M

    2016-02-27

    Withstanding 3.5 billion years of genetic drift, the canonical genetic code remains such a fundamental foundation for the complexity of life that it is highly conserved across all three phylogenetic domains. Genome engineering technologies are now making it possible to rationally change the genetic code, offering resistance to viruses, genetic isolation from horizontal gene transfer, and prevention of environmental escape by genetically modified organisms. We discuss the biochemical, genetic, and technological challenges that must be overcome in order to engineer the genetic code. PMID:26348789

  8. Overcoming Resistance to β-Lactam Antibiotics

    PubMed Central

    Worthington, Roberta J.; Melander, Christian

    2013-01-01

    β-Lactam antibiotics are one of the most important antibiotic classes but are plagued by problems of resistance and the development of new β-lactam antibiotics through side chain modification of existing β-lactam classes is not keeping pace with resistance development. In this perspective we summarize small molecule strategies to overcome resistance to β-lactam antibiotics. These approaches include the development of β-lactamase inhibitors and compounds that interfere with the ability of the bacteria to sense an antibiotic threat and activate their resistance mechanisms. PMID:23530949

  9. Overcoming Scalability Challenges for Tool Daemon Launching

    SciTech Connect

    Ahn, D H; Arnold, D C; de Supinski, B R; Lee, G L; Miller, B P; Schulz, M

    2008-02-15

    Many tools that target parallel and distributed environments must co-locate a set of daemons with the distributed processes of the target application. However, efficient and portable deployment of these daemons on large scale systems is an unsolved problem. We overcome this gap with LaunchMON, a scalable, robust, portable, secure, and general purpose infrastructure for launching tool daemons. Its API allows tool builders to identify all processes of a target job, launch daemons on the relevant nodes and control daemon interaction. Our results show that Launch-MON scales to very large daemon counts and substantially enhances performance over existing ad hoc mechanisms.

  10. Overcoming Challenges in Engineering the Genetic Code.

    PubMed

    Lajoie, M J; Söll, D; Church, G M

    2016-02-27

    Withstanding 3.5 billion years of genetic drift, the canonical genetic code remains such a fundamental foundation for the complexity of life that it is highly conserved across all three phylogenetic domains. Genome engineering technologies are now making it possible to rationally change the genetic code, offering resistance to viruses, genetic isolation from horizontal gene transfer, and prevention of environmental escape by genetically modified organisms. We discuss the biochemical, genetic, and technological challenges that must be overcome in order to engineer the genetic code.

  11. Thermal barrier research

    SciTech Connect

    Moses, K.G.

    1990-03-07

    The thermal barrier region in the TARA device is a complex arrangement combining ion-plugging by sloshing ions with an ECRH-generated thermal barrier plasma. An axisymmetric, high-mirror-ratio magnetic field, adjacent to the central cell, provides the confinement of the thermal barrier plasma and sloshing ions. This paper discusses research being done in this thermal barrier region.

  12. A Steric-inhibition model for regulation of nucleotide exchange via the Dock180 family of GEFs.

    PubMed

    Lu, Mingjian; Kinchen, Jason M; Rossman, Kent L; Grimsley, Cynthia; Hall, Matthew; Sondek, John; Hengartner, Michael O; Yajnik, Vijay; Ravichandran, Kodi S

    2005-02-22

    CDM (CED-5, Dock180, Myoblast city) family members have been recently identified as novel, evolutionarily conserved guanine nucleotide exchange factors (GEFs) for Rho-family GTPases . They regulate multiple processes, including embryonic development, cell migration, apoptotic-cell engulfment, tumor invasion, and HIV-1 infection, in diverse model systems . However, the mechanism(s) of regulation of CDM proteins has not been well understood. Here, our studies on the prototype member Dock180 reveal a steric-inhibition model for regulating the Dock180 family of GEFs. At basal state, the N-terminal SH3 domain of Dock180 binds to the distant catalytic Docker domain and negatively regulates the function of Dock180. Further studies revealed that the SH3:Docker interaction sterically blocks Rac access to the Docker domain. Interestingly, ELMO binding to the SH3 domain of Dock180 disrupted the SH3:Docker interaction, facilitated Rac access to the Docker domain, and contributed to the GEF activity of the Dock180/ELMO complex. Additional genetic rescue studies in C. elegans suggested that the regulation of the Docker-domain-mediated GEF activity by the SH3 domain and its adjoining region is evolutionarily conserved. This steric-inhibition model may be a general mechanism for regulating multiple SH3-domain-containing Dock180 family members and may have implications for a variety of biological processes.

  13. Effect of charge regulation on steric mass-action equilibrium for the ion-exchange adsorption of proteins.

    PubMed

    Shen, Hong; Frey, Douglas D

    2005-06-24

    A thermodynamic formalism is developed for incorporating the effects of charge regulation on the ion-exchange adsorption of proteins under mass-overloaded conditions as described by the steric mass-action (SMA) isotherm. To accomplish this, the pH titration behavior of a protein and the associated adsorption equilibrium of the various charged forms of a protein are incorporated into a model which also accounts for the steric hindrance of salt counterions caused by protein adsorption. For the case where the protein is dilute, the new model reduces to the protein adsorption model described recently by the authors which accounts for charge regulation. Similarly, the new model reduces to the steric mass-action isotherm developed by Brooks and Cramer which applies to mass-overloaded conditions for the case where charge regulation is ignored so that the protein has a fixed charge. Calculations using the new model were found to agree with experimental data for the adsorption of bovine serum albumin (BSA) on an anion-exchange column packing when using reasonable physical properties. The new model was also used to develop an improved theoretical criterion for determining the conditions required for an adsorbed species to displace a protein in displacement chromatography when the pH is near the protein pI.

  14. Steric hindrance regulated supramolecular assembly between β-cyclodextrin polymer and pyrene for alkaline phosphatase fluorescent sensing

    NASA Astrophysics Data System (ADS)

    Song, Chunxia; Yang, Xiaohai; Wang, Kemin; Wang, Qing; Liu, Jianbo; Huang, Jin; Zhou, Maogui; Guo, Xiaochen

    2016-03-01

    We herein report a strategy for sensitive alkaline phosphatase (ALP) fluorescent sensing based on steric hindrance regulated supramolecular assembly between β-cyclodextrin polymer (polyβ-CD) and pyrene. The fluorescence of pyrene was enhanced more than 10 times through supramolecular assembly with polyβ-CD. The 5‧-phosphorylated dsDNA probe with pyrene attached on the 3‧-terminal could be cleaved by λ exonuclease (λ exo), yielding pyrene attached on mononucleotides. Pyrene attached on mononucleotides could easily enter the cavity of polyβ-CD, resulting in fluorescence enhancement. When ALP was introduced, it could remove 5‧-phosphate groups from dsDNA and then prevented the cleavage of dsDNA. Pyrene attached on dsDNA was difficult to enter the cavity of polyβ-CD because of steric hindrance, resulting in an inconspicuous fluorescence enhancement. Owing to the excellent fluorescence enhancement during steric hindrance regulated supramolecular assembly, excellent performance of the assay method was achieved for ALP with a detection limit of 0.04 U mL- 1. The detection limit was superior or comparable with the reported methods. Besides, this method was simple in design, avoiding double-labeling of probe.

  15. Permissivity of the biphenyl-specific aerobic bacterial metabolic pathway towards analogues with various steric requirements.

    PubMed

    Overwin, Heike; Standfuß-Gabisch, Christine; González, Myriam; Méndez, Valentina; Seeger, Michael; Reichelt, Joachim; Wray, Victor; Hofer, Bernd

    2015-09-01

    It has repeatedly been shown that aryl-hydroxylating dioxygenases do not possess a very high substrate specificity. To gain more insight into this phenomenon, we examined two powerful biphenyl dioxygenases, the well-known wild-type enzyme from Burkholderia xenovorans LB400 (BphA-LB400) and a hybrid enzyme, based on a dioxygenase from Pseudomonas sp. B4-Magdeburg (BphA-B4h), for their abilities to dioxygenate a selection of eight biphenyl analogues in which the second aromatic ring was replaced by aliphatic as well as aliphatic/aromatic moieties, reflecting a variety of steric requirements. Interestingly, both enzymes were able to catalyse transformation of almost all of these compounds. While the products formed were identical, major differences were observed in transformation rates. In most cases, BphA-B4h proved to be a significantly more powerful catalyst than BphA-LB400. NMR characterization of the reaction products showed that the metabolite obtained from biphenylene underwent angular dioxygenation, whereas all other compounds were subject to lateral dioxygenation at ortho and meta carbons. Subsequent growth studies revealed that both dioxygenase source strains were able to utilize several of the biphenyl analogues as sole sources of carbon and energy. Therefore, prototype BphBCD enzymes of the biphenyl degradative pathway were examined for their ability to further catabolize the lateral dioxygenation products. All of the ortho- and meta-hydroxylated compounds were converted to acids, showing that this pathway is quite permissive, enabling catalysis of the turnover of a fairly wide variety of metabolites. PMID:26297047

  16. Interrelationship of Steric Stabilization and Self-Crowding of a Glycosylated Protein

    PubMed Central

    Høiberg-Nielsen, R.; Westh, P.; Skov, L.K.; Arleth, L.

    2009-01-01

    Abstract In the eukaryotic cell, protein glycosylation takes place in the crowded environment of the endoplasmatic reticulum. With the purpose of elucidating the impact of high concentration on the interactions of glycoproteins, we have conducted a series of small-angle x-ray scattering experiments on the heavily glycosylated enzyme Peniophora lycii phytase (Phy) and its deglycosylated counterpart (dgPhy). The small-angle x-ray scattering data were analyzed using an individual numerical form factor for each of the two glycoforms combined with two structure factors, a hard sphere and a screened coulomb potential structure factor, respectively, as determined by ab initio analysis. Based on this data analysis, three main conclusions could be drawn. First, at comparable protein concentrations (mg/ml), the relative excluded volume of Phy was ∼75% higher than that of dgPhy, showing that the glycans significantly increase excluded-volume interactions. Second, the relative excluded volume of dgPhy increased with concentration, as expected; however, the opposite effect was observed for Phy, where the relative excluded volume decreased in response to increasing protein concentration. Third, a clear difference in the effect of salinity on the excluded-volume interactions was observed between the two glycol forms. Although the relative excluded volume of dgPhy decreased with increasing ionic strength, the relative excluded volume of Phy was basically insensitive to increased salinity. We suggest that protrusion forces from the glycans contribute to steric stabilization of the protein, and that glycosylation helps to sustain repulsive electrostatic interactions under crowded conditions. In combination, this aids in stabilizing high concentrations of glycosylated proteins. PMID:19720033

  17. Steric environment around acetylcholine head groups of bolaamphiphilic nanovesicles influences the release rate of encapsulated compounds

    PubMed Central

    Stern, Avital; Guidotti, Matteo; Shaubi, Eleonora; Popov, Mary; Linder, Charles; Heldman, Eliahu; Grinberg, Sarina

    2014-01-01

    Two bolaamphiphilic compounds with identical acetylcholine (ACh) head groups, but with different lengths of an alkyl chain pendant adjacent to the head group, as well as differences between their hydrophobic skeleton, were investigated for their ability to self-assemble into vesicles that release their encapsulated content upon hydrolysis of their head groups by acetylcholinesterase (AChE). One of these bolaamphiphiles, synthesized from vernolic acid, has an alkyl chain pendant of five methylene groups, while the other, synthesized from oleic acid, has an alkyl chain pendant of eight methylene groups. Both bolaamphiphiles formed stable spherical vesicles with a diameter of about 130 nm. The ACh head groups of both bolaamphiphiles were hydrolyzed by AChE, but the hydrolysis rate was significantly faster for the bolaamphiphile with the shorter aliphatic chain pendant. Likewise, upon exposure to AChE, vesicles made from the bolaamphiphile with the shorter alkyl chain pendant released their encapsulated content faster than vesicles made from the bolaamphiphile with the longer alkyl chain pendant. Our results suggest that the steric environment around the ACh head group of bolaamphiphiles is a major factor affecting the hydrolysis rate of the head groups by AChE. Attaching an alkyl chain to the bolaamphiphile near the ACh head group allows self-assembled vesicles to form with a controlled release rate of the encapsulated materials, whereas shorter alkyl chains enable a faster head group hydrolysis, and consequently faster release, than longer alkyl chains. This principle may be implemented in the design of bolaamphiphiles for the formation of vesicles for drug delivery with desired controlled release rates. PMID:24531296

  18. Permissivity of the biphenyl-specific aerobic bacterial metabolic pathway towards analogues with various steric requirements.

    PubMed

    Overwin, Heike; Standfuß-Gabisch, Christine; González, Myriam; Méndez, Valentina; Seeger, Michael; Reichelt, Joachim; Wray, Victor; Hofer, Bernd

    2015-09-01

    It has repeatedly been shown that aryl-hydroxylating dioxygenases do not possess a very high substrate specificity. To gain more insight into this phenomenon, we examined two powerful biphenyl dioxygenases, the well-known wild-type enzyme from Burkholderia xenovorans LB400 (BphA-LB400) and a hybrid enzyme, based on a dioxygenase from Pseudomonas sp. B4-Magdeburg (BphA-B4h), for their abilities to dioxygenate a selection of eight biphenyl analogues in which the second aromatic ring was replaced by aliphatic as well as aliphatic/aromatic moieties, reflecting a variety of steric requirements. Interestingly, both enzymes were able to catalyse transformation of almost all of these compounds. While the products formed were identical, major differences were observed in transformation rates. In most cases, BphA-B4h proved to be a significantly more powerful catalyst than BphA-LB400. NMR characterization of the reaction products showed that the metabolite obtained from biphenylene underwent angular dioxygenation, whereas all other compounds were subject to lateral dioxygenation at ortho and meta carbons. Subsequent growth studies revealed that both dioxygenase source strains were able to utilize several of the biphenyl analogues as sole sources of carbon and energy. Therefore, prototype BphBCD enzymes of the biphenyl degradative pathway were examined for their ability to further catabolize the lateral dioxygenation products. All of the ortho- and meta-hydroxylated compounds were converted to acids, showing that this pathway is quite permissive, enabling catalysis of the turnover of a fairly wide variety of metabolites.

  19. Efficacy, physical properties and pharmacokinetics of sterically-stabilized liposome-encapsulated hemoglobin.

    PubMed

    Zheng, S; Zheng, Y; Beissinger, R

    1994-01-01

    We recently reported that hemoglobin (Hb) encapsulated in liposomes (LEH) containing phosphatidyl-inositol (PI) was efficacious in rats. However, liposomes containing PI may temporarily compromise mononuclear phagocytic system (MPS) function. The objective of this study was then to determine whether a polyethylene oxide derivative of phosphatidyl ethanolamine (PEG-PE) would serve as an acceptable substitute for PI in our LEH formulation. In this study we compare the physical properties, pharmacokinetics and efficacy in life support obtained for Hb encapsulated with either PI or PEG-PE phospholipids. Both liposome compositions contained the same matrix lipids, egg derived phosphatidyl choline (PC) and cholesterol, were of similar size and contained the same amount of encapsulated Hb. The liposomes differed only in their phospholipid component, one containing 5 mol% PI and the other an equal amount of the sterically-stabilizing lipid PEG-PE. The physical characteristics of the PI and PEG-PE compositions were remarkably similar: only small amounts of Met-Hb were generated during processing and following 1 month frozen storage, oxygen affinity and cooperativity and steady shear viscosity values for 30% by volume suspensions (in isotonic/isooncotic saline containing albumin) were near the normal values expected for whole blood, incubation in plasma at 37 degrees C resulted in only small amounts of Hb release and shear had very little impact on Hb leakage. Circulation half-lives following 50% isovolemic exchange-transfusion in rats were also similar, about 15-20 hours for either formation. Animals survived following 97% isovolemic exchange-transfusion of both compositions, confirming the efficacy of each. PMID:7994371

  20. Overcoming social segregation in health care in Latin America.

    PubMed

    Cotlear, Daniel; Gómez-Dantés, Octavio; Knaul, Felicia; Atun, Rifat; Barreto, Ivana C H C; Cetrángolo, Oscar; Cueto, Marcos; Francke, Pedro; Frenz, Patricia; Guerrero, Ramiro; Lozano, Rafael; Marten, Robert; Sáenz, Rocío

    2015-03-28

    Latin America continues to segregate different social groups into separate health-system segments, including two separate public sector blocks: a well resourced social security for salaried workers and their families and a Ministry of Health serving poor and vulnerable people with low standards of quality and needing a frequently impoverishing payment at point of service. This segregation shows Latin America's longstanding economic and social inequality, cemented by an economic framework that predicted that economic growth would lead to rapid formalisation of the economy. Today, the institutional setup that organises the social segregation in health care is perceived, despite improved life expectancy and other advances, as a barrier to fulfilling the right to health, embodied in the legislation of many Latin American countries. This Series paper outlines four phases in the history of Latin American countries that explain the roots of segmentation in health care and describe three paths taken by countries seeking to overcome it: unification of the funds used to finance both social security and Ministry of Health services (one public payer); free choice of provider or insurer; and expansion of services to poor people and the non-salaried population by making explicit the health-care benefits to which all citizens are entitled.

  1. Overcoming social segregation in health care in Latin America.

    PubMed

    Cotlear, Daniel; Gómez-Dantés, Octavio; Knaul, Felicia; Atun, Rifat; Barreto, Ivana C H C; Cetrángolo, Oscar; Cueto, Marcos; Francke, Pedro; Frenz, Patricia; Guerrero, Ramiro; Lozano, Rafael; Marten, Robert; Sáenz, Rocío

    2015-03-28

    Latin America continues to segregate different social groups into separate health-system segments, including two separate public sector blocks: a well resourced social security for salaried workers and their families and a Ministry of Health serving poor and vulnerable people with low standards of quality and needing a frequently impoverishing payment at point of service. This segregation shows Latin America's longstanding economic and social inequality, cemented by an economic framework that predicted that economic growth would lead to rapid formalisation of the economy. Today, the institutional setup that organises the social segregation in health care is perceived, despite improved life expectancy and other advances, as a barrier to fulfilling the right to health, embodied in the legislation of many Latin American countries. This Series paper outlines four phases in the history of Latin American countries that explain the roots of segmentation in health care and describe three paths taken by countries seeking to overcome it: unification of the funds used to finance both social security and Ministry of Health services (one public payer); free choice of provider or insurer; and expansion of services to poor people and the non-salaried population by making explicit the health-care benefits to which all citizens are entitled. PMID:25458715

  2. Barriers to Industrial Energy Efficiency - Study (Appendix A), June 2015

    SciTech Connect

    2015-06-01

    This study examines barriers that impede the adoption of energy efficient technologies and practices in the industrial sector, and identifies successful examples and opportunities to overcome these barriers. Three groups of energy efficiency technologies and measures were examined: industrial end-use energy efficiency, industrial demand response, and industrial combined heat and power. This study also includes the estimated economic benefits from hypothetical Federal energy efficiency matching grants, as directed by the Act.

  3. Barriers to Industrial Energy Efficiency - Report to Congress, June 2015

    SciTech Connect

    2015-06-01

    This report examines barriers that impede the adoption of energy efficient technologies and practices in the industrial sector, and identifies successful examples and opportunities to overcome these barriers. Three groups of energy efficiency technologies and measures were examined: industrial end-use energy efficiency, industrial demand response, and industrial combined heat and power. This report also includes the estimated economic benefits from hypothetical Federal energy efficiency matching grants, as directed by the Act.

  4. Disease management in Canada: surmounting barriers to adoption.

    PubMed

    Gallant, Christopher R; MacKinnon, Neil J; Sprague, Denise A

    2007-01-01

    Disease Management (DM) programs are used to optimize economic outcomes and improve patient outcomes. Despite this, relative to the United States, Canadian health care organizations have been slow to adopt them. The objective of this article is to examine the concept of DM programs, the existing evidence to support their use and the barriers to their adoption in Canada. Several solutions aimed at overcoming the barriers to DM in Canada are proposed.

  5. Barriers, Successes and Enabling Practices of Education for Sustainability in Far North Queensland Schools: A Case Study

    ERIC Educational Resources Information Center

    Evans, Neus; Whitehouse, Hilary; Gooch, Margaret

    2012-01-01

    There are many documented barriers to implementing school-based sustainability. This article examines a) the barriers faced by principals and staff in two regional primary schools in Far North Queensland, Australia, well known for their exemplary practice, and b) ways the barriers were overcome. Through interviews conducted with principals and key…

  6. Solid lipid nanoparticles loaded with iron to overcome barriers for treatment of iron deficiency anemia

    PubMed Central

    Hosny, Khaled Mohamed; Banjar, Zainy Mohammed; Hariri, Amani H; Hassan, Ali Habiballah

    2015-01-01

    According to the World Health Organization, 46% of the world’s children suffer from anemia, which is usually treated with iron supplements such as ferrous sulfate. The aim of this study was to prepare iron as solid lipid nanoparticles, in order to find an innovative way for alleviating the disadvantages associated with commercially available tablets. These limitations include adverse effects on the digestive system resulting in constipation and blood in the stool. The second drawback is the high variability in the absorption of iron and thus in its bioavailability. Iron solid lipid nanoparticles (Fe-SLNs) were prepared by hot homogenization/ultrasonication. Solubility of ferrous sulfate in different solid lipids was measured, and effects of process variables such as the surfactant type and concentration, homogenization and ultrasonication times, and charge-inducing agent on the particle size, zeta potential, and encapsulation efficiency were determined. Furthermore, in vitro drug release and in vivo pharmacokinetics were studied in rabbits. Results indicated that Fe-SLNs consisted of 3% Compritol 888 ATO, 1% Lecithin, 3% Poloxamer 188, and 0.2% dicetylphosphate, with an average particle size of 25 nm with 92.3% entrapment efficiency. In vivo pharmacokinetic study revealed more than fourfold enhanced bioavailability. In conclusion, Fe-SLNs could be a promising carrier for iron with enhanced oral bioavailability. PMID:25609917

  7. Overcoming the nail barrier: A systematic investigation of ungual chemical penetration enhancement.

    PubMed

    Brown, M B; Khengar, R H; Turner, R B; Forbes, B; Traynor, M J; Evans, C R G; Jones, S A

    2009-03-31

    This study investigated the in vitro nail permeability of penetrants of varying lipophilicity-caffeine (CF, logP -0.07), methylparaben (MP, logP 1.96) and terbinafine (TBF, logP 3.3) and the effect of 2 novel penetration enhancers (PEs), thioglycolic acid (TA) and urea hydrogen peroxide (urea H(2)O(2)) on their permeation. Studies were conducted using full thickness human nail clippings and ChubTur((R)) diffusion cells and penetrants were applied as saturated solutions. The rank order of steady-state penetrant flux through nails without PE application (MP>CF>TBF) suggested a greater sensitivity to penetrant molecular weight rather than logP. TA increased the flux of CF and MP approximately 4- and approximately 2-fold, respectively, whilst urea H(2)O(2) proved ineffective at enhancing permeability. The sequential application of TA followed by urea H(2)O(2) increased TBF and CF flux ( approximately 19- and approximately 4-fold, respectively) but reversing the application order of the PEs was only mildly effective at increasing just MP flux ( approximately 2-fold). Both nail PEs are likely to function via disruption of keratin disulphide bonds and the associated formation of pores that provide more 'open' drug transport channels. Effects of the PEs were penetrant specific, but the use of a reducing agent (TA) followed by an oxidising agent (urea H(2)O(2)) dramatically improved human nail penetration. PMID:19071202

  8. Electrical and electronic waste management in China: progress and the barriers to overcome.

    PubMed

    Liu, Xianbing; Tanaka, Masaru; Matsui, Yasuhiro

    2006-02-01

    Serious adverse impacts on the environment and human health from e-waste recycling have occurred in the past and continue to occur in China today, due to a lack of national management strategies. China has made great efforts to face the challenges of the approaching peak increase in the domestic generation of e-waste and the illegal shipment of e-waste from other countries. This study examined recent progress and analysed the main problems associated with this issue in China. It was found that the material and the financial flows of e-waste in China had their own specific characteristics. Nearly 60% of the generated e-wastes were sold to private individual collectors and passed into informal recycling processes. More than 90% of Chinese citizens are reluctant to pay for the recycling of their e-waste. This is due to their traditional understanding that there remained value in these end-of-life products. Regulations concerning e-waste in China have been drafted but their deficiencies are obvious. The extended producer responsibilities (EPR) have been introduced but are not well defined. Eight formal facilities have been planned and are under construction or are in operation along the eastern coast of China but it will be difficult for them to compete with the informal processes for the reasons identified during the study.

  9. Overcoming perceptions of financial barriers to rotavirus vaccine introduction in Asia

    PubMed Central

    Nelson, E Anthony S; de Quadros, Ciro A; Santosham, Mathuram; Parashar, Umesh D; Steele, A Duncan

    2013-01-01

    Despite a WHO recommendation in 2009, reaffirmed in 2013, that all countries should consider introducing rotavirus vaccines into their National Immunization Programs, as of June 2013 only 45 have done so. One major consideration appears to have been the costs of the vaccine to countries. Of concern, is that Asian countries have been slow to introduce rotavirus vaccines despite having robust data that could inform the decision-making process. Although decisions on new vaccine introduction are very complex and vary by country and region, economic evaluations are often pivotal once vaccine efficacy and safety has been established, and disease burden documented and communicated. Unfortunately, with private sector list prices of vaccines often used in economic evaluations, rather than a potential public health sector pricing structure, policy-makers may defer decisions on rotavirus vaccine introduction based on the belief that “the vaccine price is too high,” even though this might be based on erroneous data. The Pan American Health Organization’s Revolving Fund provides one example of how vaccine price can be made more competitive and transparent through a regional tendering process. Other mechanisms, such as tiered pricing and UNICEF procurement, also exist that could help Asian and other countries move forward more quickly with rotavirus vaccine introduction. PMID:23955246

  10. Women Community College Presidents: A Qualitative Approach to Exploring Leadership and Overcoming Potential Barriers

    ERIC Educational Resources Information Center

    O'Roark, Jordan J.

    2015-01-01

    Since the establishment of American higher education, the presidential profile for institutions has lacked the gender diversity in presidential leadership positions. Though women have taken positive strides as senior executive officers in higher education in the past quarter-century, the conventional post-secondary president is a white, married…

  11. Overcoming barriers to prevention, care, and treatment of hepatitis C in illicit drug users.

    PubMed

    Edlin, Brian R; Kresina, Thomas F; Raymond, Daniel B; Carden, Michael R; Gourevitch, Marc N; Rich, Josiah D; Cheever, Laura W; Cargill, Victoria A

    2005-04-15

    Injection drug use accounts for most of the incident infections with hepatitis C virus (HCV) in the United States and other developed countries. HCV infection is a complex and challenging medical condition in injection drug users (IDUs). Elements of care for hepatitis C in illicit drug users include prevention counseling and education; screening for transmission risk behavior; testing for HCV and human immunodeficiency virus infection; vaccination against hepatitis A and B viruses; evaluation for comorbidities; coordination of substance-abuse treatment services, psychiatric care, and social support; evaluation of liver disease; and interferon-based treatment for HCV infection. Caring for patients who use illicit drugs presents challenges to the health-care team that require patience, experience, and an understanding of the dynamics of substance use and addiction. Nonetheless, programs are successfully integrating hepatitis C care for IDUs into health-care settings, including primary care, methadone treatment and other substance-abuse treatment programs, infectious disease clinics, and clinics in correctional facilities. PMID:15768335

  12. Overcoming Barriers to Improve Breastfeeding Self-Efficacy in Older Adolescent Mothers

    ERIC Educational Resources Information Center

    Beattie-Fairchild, Cindy

    2013-01-01

    A lack of breastfeeding has negative consequences on mother and infant by creating health disparities with a higher incidence of morbidity and mortality. Nationwide, fewer than 60% of mothers younger than age 20 years breastfed exclusively, while fewer than 20% did so in the community being studied. The purpose of this qualitative case study was…

  13. Overcoming Barriers in Oncolytic Virotherapy with HDAC Inhibitors and Immune Checkpoint Blockade.

    PubMed

    Marchini, Antonio; Scott, Eleanor M; Rommelaere, Jean

    2016-01-06

    Oncolytic viruses (OVs) target and destroy cancer cells while sparing their normal counterparts. These viruses have been evaluated in numerous studies at both pre-clinical and clinical levels and the recent Food and Drug Administration (FDA) approval of an oncolytic herpesvirus-based treatment raises optimism that OVs will become a therapeutic option for cancer patients. However, to improve clinical outcome, there is a need to increase OV efficacy. In addition to killing cancer cells directly through lysis, OVs can stimulate the induction of anti-tumour immune responses. The host immune system thus represents a "double-edged sword" for oncolytic virotherapy: on the one hand, a robust anti-viral response will limit OV replication and spread; on the other hand, the immune-mediated component of OV therapy may be its most important anti-cancer mechanism. Although the relative contribution of direct viral oncolysis and indirect, immune-mediated oncosuppression to overall OV efficacy is unclear, it is likely that an initial period of vigorous OV multiplication and lytic activity will most optimally set the stage for subsequent adaptive anti-tumour immunity. In this review, we consider the use of histone deacetylase (HDAC) inhibitors as a means of boosting virus replication and lessening the negative impact of innate immunity on the direct oncolytic effect. We also discuss an alternative approach, aimed at potentiating OV-elicited anti-tumour immunity through the blockade of immune checkpoints. We conclude by proposing a two-phase combinatorial strategy in which initial OV replication and spread is maximised through transient HDAC inhibition, with anti-tumour immune responses subsequently enhanced by immune checkpoint blockade.

  14. Understanding and overcoming barriers to timely discharge from the pediatric units

    PubMed Central

    Mustafa, Amira; Mahgoub, Samar

    2016-01-01

    Delays in the discharge of hospital patients cause a backlog for new admissions from the Emergency Departments (ED), outpatient clinics, and transfers from the Intensive Care Units (ICU). A variety of initiatives have been reported on previously which aim to tackle this problem with variable success. In this quality improvement project, we aimed to increase the proportion of discharged patients who leave the paediatric unit by 12:00 Noon from 7% to 30% by May 2015. A baseline discharge process map was studied to understand the possible causes of the delays. A survey was conducted to look for the most likely cause for the delay. A data collection tool was designed to record the various steps in the discharge process for the pre-and post-intervention phases. Using a series of PDSA cycles, interventions were introduced. The average time for the discharge process was two hours and the baseline average percent of patients discharged by 12:00 Noon was 7% of all discharges. The leading cause for the delayed discharges was late orders by the physicians. Post-intervention, there was increase in the percentage of patients discharged by 12:00 Noon from 7% to 34%. 42% of discharged patients had appropriate reasons for afternoon discharge. By excluding these patients, the percentage of adjusted timely morning discharge has increased from 36% to 70%. Continuous monitoring and engagement of teams with regular feedback were the most important factors in achieving and sustaining improvement in the timely morning discharge of patients from our paediatric units. PMID:27752313

  15. Evolving from academic to academic entrepreneur: overcoming barriers to scientific progress and finance.

    PubMed

    Miller, Andrew D

    2016-07-01

    The overall goal of my career as an academic chemist has always been the design and creation of advanced therapeutics and diagnostics that address unmet medical need in the management of chronic diseases. Realising this goal has been an immensely difficult process involving multidisciplinary problem-driven research at the chemistry-biology-medicine interfaces. With success in the laboratory, I started seriously to question the value of remaining an academic whose career is spent in the pursuit of knowledge and understanding alone without making any significant effort to translate knowledge and understanding gained into products of genuine utility for public benefit. Therefore, I elected by choice to become an academic entrepreneur, seeking opportunities wherever possible for the translation of the best of my personal and collaborative academic research work into potentially valuable and useful products. This choice has brought with it many unexpected difficulties and challenges. Nevertheless, progress bas been made and sufficient learnt to suggest that this would be an appropriate moment to take stock and provide some personal reflections on what it takes to design and create advanced therapeutics and diagnostics in the laboratory then seek to develop, innovate and translate the best towards market.

  16. The Role of Identity Narratives in Overcoming Barriers to Parental Engagement

    ERIC Educational Resources Information Center

    Naqvi, Rahat; Carey, Jennifer; Cummins, Jim; Altidor-Brooks, Alison

    2015-01-01

    This paper describes a qualitative study conducted over the course of one school year in an ethnically diverse school. Aimed at exploring the conditions under which parents of low socioeconomic status (SES) immigrant-background children will engage actively with the school, we involved parents and facilitators in story-telling sessions, sharing…

  17. Videos Bridging Asia and Africa: Overcoming Cultural and Institutional Barriers in Technology-Mediated Rural Learning

    ERIC Educational Resources Information Center

    Van Mele, Paul; Wanvoeke, Jonas; Akakpo, Cyriaque; Dacko, Rosaline Maiga; Ceesay, Mustapha; Beavogui, Louis; Soumah, Malick; Anyang, Robert

    2010-01-01

    Will African farmers watch and learn from videos featuring farmers in Bangladesh? Learning videos on rice seed management were made with rural women in Bangladesh. By using a new approach, called zooming-in, zooming-out, the videos were of regional relevance and locally appropriate. When the Africa Rice Center (AfricaRice) introduced them to…

  18. Sexual History-Taking: Using Educational Interventions to Overcome Barriers to Learning

    ERIC Educational Resources Information Center

    Jayasuriya, Ashini N.; Dennick, Reg

    2011-01-01

    Sexual history-taking is a basic medical skill that is traditionally taught poorly in medical school. Practising medical professionals have frequently reported feeling inadequately trained at taking these histories or discussing sexual risk. In order to promote and enhance the learning of this basic skill, those who teach sexual history-taking…

  19. Overcoming the Barrier of Low Efficiency during Genetic Transformation of Streptococcus mitis

    PubMed Central

    Salvadori, Gabriela; Junges, Roger; Morrison, Donald A.; Petersen, Fernanda C.

    2016-01-01

    Objective: Streptococcus mitis is a predominant oral colonizer, but difficulties in genetic manipulation of this species have hampered our understanding of the mechanisms it uses for colonization of oral surfaces. The aim of this study was to reveal optimal conditions for natural genetic transformation in S. mitis and illustrate its application in direct genome editing. Methods: Luciferase reporter assays were used to assess gene expression of the alternative sigma factor (σX) in combination with natural transformation experiments to evaluate the efficiency by which S. mitis activates the competence system and incorporates exogenous DNA. Optimal amounts and sources of donor DNA (chromosomal, amplicon, or replicative plasmid), concentrations of synthetic competence-stimulating peptide, and transformation media were assessed. Results: A semi-defined medium showed much improved results for response to the competence stimulating peptide when compared to rich media. The use of a donor amplicon with large homology flanking regions also provided higher transformation rates. Overall, an increase of transformation efficiencies from 0.001% or less to over 30% was achieved with the developed protocol. We further describe the construction of a markerless mutant based on this high efficiency strategy. Conclusion: We optimized competence development in S. mitis, by use of semi-defined medium and appropriate concentrations of synthetic competence factor. Combined with the use of a large amplicon of donor DNA, this method allowed easy and direct editing of the S. mitis genome, broadening the spectrum of possible downstream applications of natural transformation in this species. PMID:27458432

  20. Overcoming Medicaid Reimbursement Barriers to Funding School Nursing Services for Low-Income Children with Asthma

    ERIC Educational Resources Information Center

    Malcarney, Mary-Beth; Horton, Katherine; Seiler, Naomi

    2016-01-01

    Background: School nurses can provide direct services for children with asthma, educate, and reinforce treatment recommendations to children and their families, and coordinate the school-wide response to students' asthma emergencies. Unfortunately, school-based health services today depend on an unreliable patchwork of funding. Limited state and…

  1. Overcoming the Barriers to Uptake: A Study of 6 Danish Health-Based Serious Games Projects

    ERIC Educational Resources Information Center

    Brown, Damian

    2013-01-01

    Serious gaming for health benefits is moving out of the realm of being potentially interesting, and the authors are starting to see a growing maturity in the field. This study of six serious gaming projects based either wholly or partly in Denmark investigates the changes taking place in the healthcare area based on experiences with serious gaming…

  2. Using synthetic biology to distinguish and overcome regulatory and functional barriers related to nitrogen fixation.

    PubMed

    Wang, Xia; Yang, Jian-Guo; Chen, Li; Wang, Ji-Long; Cheng, Qi; Dixon, Ray; Wang, Yi-Ping

    2013-01-01

    Biological nitrogen fixation is a complex process requiring multiple genes working in concert. To date, the Klebsiella pneumoniae nif gene cluster, divided into seven operons, is one of the most studied systems. Its nitrogen fixation capacity is subject to complex cascade regulation and physiological limitations. In this report, the entire K. pneumoniae nif gene cluster was reassembled as operon-based BioBrick parts in Escherichia coli. It provided ~100% activity of native K. pneumoniae system. Based on the expression levels of these BioBrick parts, a T7 RNA polymerase-LacI expression system was used to replace the σ(54)-dependent promoters located upstream of nif operons. Expression patterns of nif operons were critical for the maximum activity of the recombinant system. By mimicking these expression levels with variable-strength T7-dependent promoters, ~42% of the nitrogenase activity of the σ(54)-dependent nif system was achieved in E. coli. When the newly constructed T7-dependent nif system was challenged with different genetic and physiological conditions, it bypassed the original complex regulatory circuits, with minor physiological limitations. Therefore, we have successfully replaced the nif regulatory elements with a simple expression system that may provide the first step for further research of introducing nif genes into eukaryotic organelles, which has considerable potentials in agro-biotechnology.

  3. Confidence-Based Learning CME: Overcoming Barriers in Irritable Bowel Syndrome with Constipation

    ERIC Educational Resources Information Center

    Cash, Brooks; Mitchner, Natasha A.; Ravyn, Dana

    2011-01-01

    Introduction: Performance of health care professionals depends on both medical knowledge and the certainty with which they possess it. Conventional continuing medical education interventions assess the correctness of learners' responses but do not determine the degree of confidence with which they hold incorrect information. This study describes…

  4. Strategies for Overcoming Barriers Inherent in Cross-Cultural Research (Doing Research).

    ERIC Educational Resources Information Center

    Jameson, Daphne A.

    1994-01-01

    Raises concerns about unexamined conceptual assumptions and over-generalizations of research findings in the comparative management area. Suggests two ways of combating these problems: collaboration and accounting for complexities of culture. (SR)

  5. FREESTYLE: Reducing Barriers to Personal Success by Overcoming Sex-Role Stereotypes.

    ERIC Educational Resources Information Center

    Seeley, Pat

    "Freestyle," a new television series, is designed to expand career awareness of children ages 9 through 12 and reduce the limiting effects of sex role and ethnic stereotyping. The series is a product of the Television Career Awareness Project (TV CAP), a consortium of six agencies funded by a grant from the National Institute of Education (NIE).…

  6. Tropism-modified AAV Vectors Overcome Barriers to Successful Cutaneous Therapy

    PubMed Central

    Sallach, Jessica; Di Pasquale, Giovanni; Larcher, Fernando; Niehoff, Nadine; Rübsam, Matthias; Huber, Anke; Chiorini, Jay; Almarza, David; Eming, Sabine A; Ulus, Hikmet; Nishimura, Stephen; Hacker, Ulrich T; Hallek, Michael; Niessen, Carien M; Büning, Hildegard

    2014-01-01

    Autologous human keratinocytes (HK) forming sheet grafts are approved as skin substitutes. Genetic engineering of HK represents a promising technique to improve engraftment and survival of transplants. Although efficacious in keratinocyte-directed gene transfer, retro-/lentiviral vectors may raise safety concerns when applied in regenerative medicine. We therefore optimized adeno-associated viral (AAV) vectors of the serotype 2, characterized by an excellent safety profile, but lacking natural tropism for HK, through capsid engineering. Peptides, selected by AAV peptide display, engaged novel receptors that increased cell entry efficiency by up to 2,500-fold. The novel targeting vectors transduced HK with high efficiency and a remarkable specificity even in mixed cultures of HK and feeder cells. Moreover, differentiated keratinocytes in organotypic airlifted three-dimensional cultures were transduced following topical vector application. By exploiting comparative gene analysis we further succeeded in identifying αvβ8 integrin as a target receptor thus solving a major challenge of directed evolution approaches and describing a promising candidate receptor for cutaneous gene therapy. PMID:24468915

  7. Overcoming the nail barrier: A systematic investigation of ungual chemical penetration enhancement.

    PubMed

    Brown, M B; Khengar, R H; Turner, R B; Forbes, B; Traynor, M J; Evans, C R G; Jones, S A

    2009-03-31

    This study investigated the in vitro nail permeability of penetrants of varying lipophilicity-caffeine (CF, logP -0.07), methylparaben (MP, logP 1.96) and terbinafine (TBF, logP 3.3) and the effect of 2 novel penetration enhancers (PEs), thioglycolic acid (TA) and urea hydrogen peroxide (urea H(2)O(2)) on their permeation. Studies were conducted using full thickness human nail clippings and ChubTur((R)) diffusion cells and penetrants were applied as saturated solutions. The rank order of steady-state penetrant flux through nails without PE application (MP>CF>TBF) suggested a greater sensitivity to penetrant molecular weight rather than logP. TA increased the flux of CF and MP approximately 4- and approximately 2-fold, respectively, whilst urea H(2)O(2) proved ineffective at enhancing permeability. The sequential application of TA followed by urea H(2)O(2) increased TBF and CF flux ( approximately 19- and approximately 4-fold, respectively) but reversing the application order of the PEs was only mildly effective at increasing just MP flux ( approximately 2-fold). Both nail PEs are likely to function via disruption of keratin disulphide bonds and the associated formation of pores that provide more 'open' drug transport channels. Effects of the PEs were penetrant specific, but the use of a reducing agent (TA) followed by an oxidising agent (urea H(2)O(2)) dramatically improved human nail penetration.

  8. Overcoming the organization-practice barrier in sports injury prevention: A nonhierarchical organizational model.

    PubMed

    Dahlström, Ö; Jacobsson, J; Timpka, T

    2015-08-01

    The organization of sports at the national level has seldom been included in scientific discussions of sports injury prevention. The aim of this study was to develop a model for organization of sports that supports prevention of overuse injuries. The quality function deployment technique was applied in seminars over a two-season period to develop a national organizational structure for athletics in Sweden that facilitates prevention of overuse injuries. Three central features of the resulting model for organization of sports at the national level are (a) diminishment of the organizational hierarchy: participatory safety policy design is introduced through annual meetings where actors from different sectors of the sporting community discuss training, injury prevention, and sports safety policy; (b) introduction of a safety surveillance system: a ubiquitous system for routine collection of injury and illness data; and (c) an open forum for discussion of safety issues: maintenance of a safety forum for participants from different sectors of the sport. A nonhierarchical model for organization of sports at the national level - facilitated by modern information technology - adapted for the prevention of overuse injuries has been developed. Further research is warranted to evaluate the new organizational model in prospective effectiveness studies.

  9. Evolving from academic to academic entrepreneur: overcoming barriers to scientific progress and finance.

    PubMed

    Miller, Andrew D

    2016-07-01

    The overall goal of my career as an academic chemist has always been the design and creation of advanced therapeutics and diagnostics that address unmet medical need in the management of chronic diseases. Realising this goal has been an immensely difficult process involving multidisciplinary problem-driven research at the chemistry-biology-medicine interfaces. With success in the laboratory, I started seriously to question the value of remaining an academic whose career is spent in the pursuit of knowledge and understanding alone without making any significant effort to translate knowledge and understanding gained into products of genuine utility for public benefit. Therefore, I elected by choice to become an academic entrepreneur, seeking opportunities wherever possible for the translation of the best of my personal and collaborative academic research work into potentially valuable and useful products. This choice has brought with it many unexpected difficulties and challenges. Nevertheless, progress bas been made and sufficient learnt to suggest that this would be an appropriate moment to take stock and provide some personal reflections on what it takes to design and create advanced therapeutics and diagnostics in the laboratory then seek to develop, innovate and translate the best towards market. PMID:27476702

  10. Informed Courage in Local Leadership: Essential in Overcoming Barriers to Change in Education.

    ERIC Educational Resources Information Center

    VanSciver, James H.

    Without fear, there is no courage, only ignorance of a situation's dynamics. Acknowledging a decision's liabilities promotes fear and forces the educational leader to exercise courage in formulating and carrying out a response to that situation. Courage alone is not enough, however, and could lead to professional suicide. Wisdom to marshal that…

  11. Mobile "Comfort" Zones: Overcoming Barriers to Enable Facilitated Learning in the Workplace

    ERIC Educational Resources Information Center

    Holley, Debbie; Sentance, Sue

    2015-01-01

    The affordances of mobile technologies are well documented (Vavoula (2004); Wali (2008); Pachler et al (2010); Cook (2011); Sharples (2013). Linked with the rapid expansion of the "SMART" phones, where users access fast/high quality information, new opportunities are offered to engage students at a time/place of their own choosing. Our…

  12. Overcoming Language and Literacy Barriers in Safety and Health Training of Agricultural Workers

    PubMed Central

    Arcury, Thomas A.; Estrada, Jorge M.; Quandt, Sara A.

    2010-01-01

    The workforce in all areas of United States agriculture and forestry is becoming increasingly diverse in language, culture, and education. Many agricultural workers are immigrants who have limited English language skills and limited educational attainment. Providing safety and health training to this large, diverse, dispersed, and often transient population of workers is challenging. This review, prepared for the 2010 Agricultural Safety and Health Council of America/National Institute for Occupational Safety and Health conference, “Be Safe, Be Profitable: Protecting Workers in Agriculture,” is divided into five sections. First, we describe the occupational and demographic characteristics of agricultural workers in the US to highlight their safety and health training needs. Second, we summarize current research on the social and cultural attributes of agricultural workers and agricultural employers that affect the provision of safety and health training. Worker and employer attributes include language, literacy, financial limitations, work beliefs, and health beliefs. Third, we review current initiatives addressing safety and health training for agricultural workers that consider worker language and literacy. These initiatives are limited to a few specific topics (e.g., pesticides, heat stress); they do not provide general programs of safety training that would help establish a culture of workplace safety. However, several innovative approaches to health and safety training are being implemented, including the use of community-based participatory approaches and lay health promoter programs. Fourth, the limited industry response for safety training with this linguistically diverse and educationally limited workforce is summarized. Finally, gaps in knowledge and practice are summarized and recommendations to develop educationally, culturally, and linguistically appropriate safety and health training are presented. PMID:20665309

  13. Overcoming Psychosocial Barriers to Maternal Exercise: Intervention Strategies to Improve Participation and Adherence

    ERIC Educational Resources Information Center

    Schoenfeld, Brad; Tiryaki-Sonmez, Gul

    2011-01-01

    Poor adherence to physical activity programmes during pregnancy is a serious national issue, one that has detrimental effects on a large percentage of the population. Not only does a lack of activity result in a decrease in quality of life for women during term, but the effects can carry over well after pregnancy, potentially leading to increased…

  14. Overcoming Barriers in Oncolytic Virotherapy with HDAC Inhibitors and Immune Checkpoint Blockade

    PubMed Central

    Marchini, Antonio; Scott, Eleanor M.; Rommelaere, Jean

    2016-01-01

    Oncolytic viruses (OVs) target and destroy cancer cells while sparing their normal counterparts. These viruses have been evaluated in numerous studies at both pre-clinical and clinical levels and the recent Food and Drug Administration (FDA) approval of an oncolytic herpesvirus-based treatment raises optimism that OVs will become a therapeutic option for cancer patients. However, to improve clinical outcome, there is a need to increase OV efficacy. In addition to killing cancer cells directly through lysis, OVs can stimulate the induction of anti-tumour immune responses. The host immune system thus represents a “double-edged sword” for oncolytic virotherapy: on the one hand, a robust anti-viral response will limit OV replication and spread; on the other hand, the immune-mediated component of OV therapy may be its most important anti-cancer mechanism. Although the relative contribution of direct viral oncolysis and indirect, immune-mediated oncosuppression to overall OV efficacy is unclear, it is likely that an initial period of vigorous OV multiplication and lytic activity will most optimally set the stage for subsequent adaptive anti-tumour immunity. In this review, we consider the use of histone deacetylase (HDAC) inhibitors as a means of boosting virus replication and lessening the negative impact of innate immunity on the direct oncolytic effect. We also discuss an alternative approach, aimed at potentiating OV-elicited anti-tumour immunity through the blockade of immune checkpoints. We conclude by proposing a two-phase combinatorial strategy in which initial OV replication and spread is maximised through transient HDAC inhibition, with anti-tumour immune responses subsequently enhanced by immune checkpoint blockade. PMID:26751469

  15. Identifying, Understanding, and Overcoming Barriers to the Use of Clinical Practice Guidelines in Pediatric Oncology

    ClinicalTrials.gov

    2016-07-25

    B-Cell Non-Hodgkin Lymphoma; Chemotherapy-Related Nausea and/or Vomiting; Childhood Acute Myeloid Leukemia; Childhood Burkitt Lymphoma; Childhood Neoplasm; Febrile Neutropenia; Hematopoietic Cell Transplantation Recipient; Recurrent Childhood Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

  16. Education for All Aspects of the Industry: Overcoming Barriers to Broad-Based Training.

    ERIC Educational Resources Information Center

    Bailey, Thomas; And Others

    This report is designed to help the educational community develop the "all aspects of the industry" (AAI) strategy promoted in the Perkins Vocational Education Act. The introduction describes the current status of AAI and elaborates on three arguments for it: (1) AAI is a pedagogic strategy that promotes more effective learning; (2) better…

  17. Overcoming language and literacy barriers in safety and health training of agricultural workers.

    PubMed

    Arcury, Thomas A; Estrada, Jorge M; Quandt, Sara A

    2010-07-01

    The workforce in all areas of United States agriculture and forestry is becoming increasingly diverse in language, culture, and education. Many agricultural workers are immigrants who have limited English language skills and limited educational attainment. Providing safety and health training to this large, diverse, dispersed, and often transient population of workers is challenging. This review, prepared for the 2010 Agricultural Safety and Health Council of America/National Institute for Occupational Safety and Health conference, "Be Safe, Be Profitable: Protecting Workers in Agriculture," is divided into five sections. First, we describe the occupational and demographic characteristics of agricultural workers in the United States to highlight their safety and health training needs. Second, we summarize current research on the social and cultural attributes of agricultural workers and agricultural employers that affect the provision of safety and health training. Worker and employer attributes include language, literacy, financial limitations, work beliefs, and health beliefs. Third, we review current initiatives addressing safety and health training for agricultural workers that consider worker language and literacy. These initiatives are limited to a few specific topics (e.g., pesticides, heat stress); they do not provide general programs of safety training that would help establish a culture of workplace safety. However, several innovative approaches to health and safety training are being implemented, including the use of community-based participatory approaches and lay health promoter programs. Fourth, the limited industry response for safety training with this linguistically diverse and educationally limited workforce is summarized. Finally, gaps in knowledge and practice are summarized and recommendations to develop educationally, culturally, and linguistically appropriate safety and health training are presented. PMID:20665309

  18. Overcoming Language and Cultural Barriers in School: Helping Hispanic Students Acquire Success in Elementary School

    ERIC Educational Resources Information Center

    Ivey, Pauline S.

    2011-01-01

    Research shows that Hispanic second language students are not as successful as their English-speaking peers in school. The problem is in part due to several factors: curriculum deliverance in a foreign language, cultural differences, and family/school disconnect. Current census reports reveal that Hispanic populations in the United States, and…

  19. Advancing superwindows in the United States: overcoming technical and institutional barriers

    NASA Astrophysics Data System (ADS)

    Arasteh, Dariush

    1992-11-01

    Simulation studies have shown that windows with total U-values under 0.8 W/m2-C and solar heat gain coefficients greater than 0.5 will admit more useful solar heat gain than they will loose by conduction/convection and radiation in virtually all locations in the continental United States, independent of orientation. Such fenestration products, when used in typical homes, thus become net energy gainers. Laboratory and field testing/simulations conducted as part of LBL's superwindow research program have proven that glazing systems with three glazing layers, two low-emissivity coatings, and the appropriate low-conductivity gas-fill can achieve this performance level. Beginning in 1990 several U.S. manufacturers started to offer such products commercially. However, laboratory and field testing, as well as computer simulations, have also shown that existing frame/edge designs and materials significantly reduce the total performance of windows using such superglazings. Current research focuses on the use of simulation tools and a high resolution laboratory infrared thermography imaging system to work with manufacturers to develop highly insulating frames and edges.

  20. Registered Apprenticeships in Nontraditional Occupations for Florida's Women: Accessing Opportunities and Overcoming Barriers. 1998 Annual Report.

    ERIC Educational Resources Information Center

    University of Central Florida, Orlando. Coll. of Education.

    During 1997-1998, the Florida Education and Employment Council for Women and Girls has continued an analysis of strategies to assist all Florida women in achieving self-sufficiency. As part of that effort, the council examined registered apprenticeship programs as an avenue of on-the-job training offering women, as well as men, high-skilled,…

  1. Overcoming Barriers: Tailoring Climate Education for Latino and non-Latino Citizen to Impact Decision Making

    NASA Astrophysics Data System (ADS)

    Estrada, M.; Boudrias, M. A.; Silva-Send, N. J.; Gershunov, A.; Anders, S.

    2013-12-01

    Culture has been shown to be an important determinant of Latino/Hispanic American environmental attitudes (Schultz, Unipan, & Gamba, 2000), which might help to explain the underrepresentation of Latinos in the U.S. 'environmental' movement. With shifting U.S. demographics, however, there is increased urgency to understand how Latinos integrate into the community that is concerned and literate about climate change. As part of the Climate Education Partners (CEP) work in San Diego, we investigated how to address this ethnic group disparity. In this paper, we describe a study of how climate change science knowledge relates to Latino and Non-Latino citizen (a) engagement in conservation behaviors and (b) more informed decision-making. Drawing upon previous work on the Tripartite Integration Model of Social Influence (TIMSI) (Estrada et al., 2011), we hypothesized that climate change knowledge that promotes efficacy (i.e., a sense that one can do something) would relate to greater engagement in conservation behaviors and more informed decision-making (both common of community members concerned about climate change). To test this model, 1001 San Diego residence participated in a telephone survey in which the attitudes towards climate change were assessed using '6 Americas' segmentation (Leiserowitz et al., 2011), in addition to climate change science knowledge, efficacy, values, and engagement in weekly and yearly climate change friendly behaviors (e.g., conservation, transportation, community engagement behaviors). Results showed that there were significant differences in the 6 America segmentation distributions, knowledge, efficacy and behavioral engagement with Latinos significantly more concerned than Non-Latinos, and reporting greater knowledge, efficacy and engagement in behaviors. However, data from both groups showed support for the TIMSI theoretical framework, such that efficacy mediated the relationship between climate change knowledge and behavior. Thus, for both groups, climate change science knowledge was more likely to result in behavioral engagement when the science knowledge was accompanied with the belief that one has the ability to engage in behaviors that mitigate or adapt to climate change (i.e., efficacy). Implications for how to improve both Latino and Non-Latino climate change education that results in informed decision-making and greater integration into the community concerned about climate change will be discussed.

  2. Overcoming the Language Barrier. Third European Congress on Information Systems and Networks, Vol. 1.

    ERIC Educational Resources Information Center

    Commission des Communautes Europeennes (Luxembourg).

    The papers presented here have a double objective: to give those responsible for the Action plan for the improvement of information transfer between European languages a good view of existing and developing systems and to make future users of EURONET acquainted with methods and tools that will soon be available. The papers are arranged under six…

  3. Overcoming Barriers to Prevention, Care, and Treatment of Hepatitis C in Illicit Drug Users

    PubMed Central

    Edlin, Brian R.; Kresina, Thomas F.; Raymond, Daniel B.; Carden, Michael R.; Gourevitch, Marc N.; Rich, Josiah D.; Cheever, Laura W.; Cargill, Victoria A.

    2005-01-01

    Injection drug use accounts for most of the incident infections with hepatitis C virus (HCV) in the United States and other developed countries. HCV infection is a complex and challenging medical condition in injection drug users (IDUs). Elements of care for hepatitis C in illicit drug users include prevention counseling and education; screening for transmission risk behavior; testing for HCV and human immunodeficiency virus infection; vaccination against hepatitis A and B viruses; evaluation for comorbidities; coordination of substance-abuse treatment services, psychiatric care, and social support; evaluation of liver disease; and interferon-based treatment for HCV infection. Caring for patients who use illicit drugs presents challenges to the health-care team that require patience, experience, and an understanding of the dynamics of substance use and addiction. Nonetheless, programs are successfully integrating hepatitis C care for IDUs into health-care settings, including primary care, methadone treatment and other substance-abuse treatment programs, infectious disease clinics, and clinics in correctional facilities. PMID:15768335

  4. Systems approach-based mitigation of postharvest diseases to overcome trade barriers for Washington apples

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Speck rot caused by Phacidiopycnis washingtonensis and Sphaeropsis rot caused by S. pyriputrescens were reported as new postharvest fruit rot diseases in Washington State in the mid-2000s. Both diseases can cause significant postharvest losses of fruit if left uncontrolled, and the two fungi have be...

  5. Working with Schools in Identifying and Overcoming Emotional Barriers to Learning

    ERIC Educational Resources Information Center

    Nash, Poppy; Schlösser, Annette

    2015-01-01

    This paper reports a case study on working closely with a secondary school, to enhance understanding of disruptive behaviour, through the use of bespoke Continuing Professional Development (CPD) materials. This project evolved from the researchers' previous research on the extent to which teachers believe disruptive pupils can control their…

  6. Cargo surface hydrophobicity is sufficient to overcome the nuclear pore complex selectivity barrier.

    PubMed

    Naim, Bracha; Zbaida, David; Dagan, Shlomi; Kapon, Ruti; Reich, Ziv

    2009-09-16

    To fulfil their function, nuclear pore complexes (NPCs) must discriminate between inert proteins and nuclear transport receptors (NTRs), admitting only the latter. This specific permeation is thought to depend on interactions between hydrophobic patches on NTRs and phenylalanine-glycine (FG) or related repeats that line the NPC. Here, we tested this premise directly by conjugating different hydrophobic amino-acid analogues to the surface of an inert protein and examining its ability to cross NPCs unassisted by NTRs. Conjugation of as few as four hydrophobic moieties was sufficient to enable passage of the protein through NPCs. Transport of the modified protein proceeded with rates comparable to those measured for the innate protein when bound to an NTR and was relatively insensitive both to the nature and density of the amino acids used to confer hydrophobicity. The latter observation suggests a non-specific, small, and plant interaction network between cargo and FG repeats.

  7. Older Teens in TANF Families: Overcoming Barriers to Self-Sufficiency.

    ERIC Educational Resources Information Center

    Kaplan, Jan

    2001-01-01

    Older teens living in families receiving Temporary Assistance to Needy Families (TANF) face serious sociodemographic disadvantages. When combined with the characteristic risk-taking behaviors of adolescence, these disadvantages pose a threat to TANF teens' immediate and future physical, psychological, and emotional health and to their long-term…

  8. Restaurant employees' perceptions of barriers to three food safety practices.

    PubMed

    Howells, Amber D; Roberts, Kevin R; Shanklin, Carol W; Pilling, Valerie K; Brannon, Laura A; Barrett, Betsy B

    2008-08-01

    Limited research has been conducted to assess employees' perceptions of barriers to implementing food safety practices. Focus groups were conducted with two groups of restaurant employees to identify perceived barriers to implementing three food safety practices: handwashing, using thermometers, and cleaning work surfaces. Ten focus groups were conducted with 34 employees who did not receive training (Group A). Twenty focus groups were conducted with 125 employees after they had participated in a formal ServSafe training program (Group B). The following barriers were identified in at least one focus group in both Group A and Group B for all three practices: time constraints, inconvenience, inadequate training, and inadequate resources. In Group A, additional barriers identified most often were a lack of space and other tasks competing with cleaning work surfaces; inconvenient location of sinks and dry skin from handwashing; and lack of working thermometers and thermometers in inconvenient locations. Additional barriers identified most often by Group B were no incentive to do it and the manager not monitoring whether employees cleaned work surfaces; inconvenient location of sinks and dry skin from handwashing; and lack of working thermometers and manager not monitoring the use of thermometers. Results will be used to develop and implement interventions to overcome perceived barriers that training appears not to address. Knowledge of perceived barriers among employees can assist food and nutrition professionals in facilitating employees in overcoming these barriers and ultimately improve compliance with food safety practices.

  9. Restaurant employees' perceptions of barriers to three food safety practices.

    PubMed

    Howells, Amber D; Roberts, Kevin R; Shanklin, Carol W; Pilling, Valerie K; Brannon, Laura A; Barrett, Betsy B

    2008-08-01

    Limited research has been conducted to assess employees' perceptions of barriers to implementing food safety practices. Focus groups were conducted with two groups of restaurant employees to identify perceived barriers to implementing three food safety practices: handwashing, using thermometers, and cleaning work surfaces. Ten focus groups were conducted with 34 employees who did not receive training (Group A). Twenty focus groups were conducted with 125 employees after they had participated in a formal ServSafe training program (Group B). The following barriers were identified in at least one focus group in both Group A and Group B for all three practices: time constraints, inconvenience, inadequate training, and inadequate resources. In Group A, additional barriers identified most often were a lack of space and other tasks competing with cleaning work surfaces; inconvenient location of sinks and dry skin from handwashing; and lack of working thermometers and thermometers in inconvenient locations. Additional barriers identified most often by Group B were no incentive to do it and the manager not monitoring whether employees cleaned work surfaces; inconvenient location of sinks and dry skin from handwashing; and lack of working thermometers and manager not monitoring the use of thermometers. Results will be used to develop and implement interventions to overcome perceived barriers that training appears not to address. Knowledge of perceived barriers among employees can assist food and nutrition professionals in facilitating employees in overcoming these barriers and ultimately improve compliance with food safety practices. PMID:18656574

  10. Nanoparticle delivery of sterically hindered platinum(IV) prodrugs shows 100 times higher potency than that of cisplatin upon light activation.

    PubMed

    Song, Haiqin; Kang, Xiang; Sun, Jing; Jing, Xiabin; Wang, Zehua; Yan, Lesan; Qi, Ruogu; Zheng, Minhua

    2016-02-01

    The introduction of a sterically hindered pyridine ligand to a photosensitive platinum(iv) drug for drug delivery resulted in a >100 fold increase in effectiveness compared to the gold standard, cisplatin. PMID:26727577

  11. Overcoming Multidrug Resistance in Cancer Stem Cells

    PubMed Central

    Moitra, Karobi

    2015-01-01

    The principle mechanism of protection of stem cells is through the expression of ATP-binding cassette (ABC) transporters. These transporters serve as the guardians of the stem cell population in the body. Unfortunately these very same ABC efflux pumps afford protection to cancer stem cells in tumors, shielding them from the adverse effects of chemotherapy. A number of strategies to circumvent the function of these transporters in cancer stem cells are currently under investigation. These strategies include the development of competitive and allosteric modulators, nanoparticle mediated delivery of inhibitors, targeted transcriptional regulation of ABC transporters, miRNA mediated inhibition, and targeting of signaling pathways that modulate ABC transporters. The role of ABC transporters in cancer stem cells will be explored in this paper and strategies aimed at overcoming drug resistance caused by these particular transporters will also be discussed. PMID:26649310

  12. T7 replisome directly overcomes DNA damage

    NASA Astrophysics Data System (ADS)

    Sun, Bo; Pandey, Manjula; Inman, James T.; Yang, Yi; Kashlev, Mikhail; Patel, Smita S.; Wang, Michelle D.

    2015-12-01

    Cells and viruses possess several known `restart' pathways to overcome lesions during DNA replication. However, these `bypass' pathways leave a gap in replicated DNA or require recruitment of accessory proteins, resulting in significant delays to fork movement or even cell division arrest. Using single-molecule and ensemble methods, we demonstrate that the bacteriophage T7 replisome is able to directly replicate through a leading-strand cyclobutane pyrimidine dimer (CPD) lesion. We show that when a replisome encounters the lesion, a substantial fraction of DNA polymerase (DNAP) and helicase stay together at the lesion, the replisome does not dissociate and the helicase does not move forward on its own. The DNAP is able to directly replicate through the lesion by working in conjunction with helicase through specific helicase-DNAP interactions. These observations suggest that the T7 replisome is fundamentally permissive of DNA lesions via pathways that do not require fork adjustment or replisome reassembly.

  13. T7 replisome directly overcomes DNA damage

    PubMed Central

    Sun, Bo; Pandey, Manjula; Inman, James T.; Yang, Yi; Kashlev, Mikhail; Patel, Smita S.; Wang, Michelle D.

    2015-01-01

    Cells and viruses possess several known ‘restart' pathways to overcome lesions during DNA replication. However, these ‘bypass' pathways leave a gap in replicated DNA or require recruitment of accessory proteins, resulting in significant delays to fork movement or even cell division arrest. Using single-molecule and ensemble methods, we demonstrate that the bacteriophage T7 replisome is able to directly replicate through a leading-strand cyclobutane pyrimidine dimer (CPD) lesion. We show that when a replisome encounters the lesion, a substantial fraction of DNA polymerase (DNAP) and helicase stay together at the lesion, the replisome does not dissociate and the helicase does not move forward on its own. The DNAP is able to directly replicate through the lesion by working in conjunction with helicase through specific helicase–DNAP interactions. These observations suggest that the T7 replisome is fundamentally permissive of DNA lesions via pathways that do not require fork adjustment or replisome reassembly. PMID:26675048

  14. Innovative Strategies to Overcome Biofilm Resistance

    PubMed Central

    Taraszkiewicz, Aleksandra; Fila, Grzegorz; Grinholc, Mariusz; Nakonieczna, Joanna

    2013-01-01

    We review the recent literature concerning the efficiency of antimicrobial photodynamic inactivation toward various microbial species in planktonic and biofilm cultures. The review is mainly focused on biofilm-growing microrganisms because this form of growth poses a threat to chronically infected or immunocompromised patients and is difficult to eradicate from medical devices. We discuss the biofilm formation process and mechanisms of its increased resistance to various antimicrobials. We present, based on data in the literature, strategies for overcoming the problem of biofilm resistance. Factors that have potential for use in increasing the efficiency of the killing of biofilm-forming bacteria include plant extracts, enzymes that disturb the biofilm structure, and other nonenzymatic molecules. We propose combining antimicrobial photodynamic therapy with various antimicrobial and antibiofilm approaches to obtain a synergistic effect to permit efficient microbial growth control at low photosensitizer doses. PMID:23509680

  15. Overcoming the effects of intentional forgetting.

    PubMed

    Lehman, Melissa; Malmberg, Kenneth J

    2011-02-01

    The long-term effects of the compartmentalization of task-irrelevant memories were investigated using a directed forgetting procedure. Many models tacitly assume the persistence of the costs and benefits of directed forgetting or otherwise fail to predict what factors might reduce or eliminate them. In contrast, a retrieving effectively from memory model (REM; Lehman & Malmberg, 2009) predicts that intentional forgetting should only be observed for free recall when temporal context is used to probe memory. By manipulating whether study lists were constructed from category exemplars or from a random set of words, and by either providing temporal or category cues at test, we tested the prediction. The effects of directed forgetting were eliminated when categorized lists were studied and category cues were provided. When categorized lists were used but category cues were not provided, the usual costs and benefits of directed forgetting were observed. These results specify the conditions under which the consequences of intentional forgetting can be overcome. PMID:21264615

  16. Acylmethyl(aryl)tellurium(IV,II) derivatives: intramolecular secondary bonding and steric rigidity.

    PubMed

    Chauhan, Ashok K S; Singh, Puspendra; Srivastava, Ramesh C; Duthie, Andrew; Voda, Andreea

    2008-08-14

    Electrophilic substitution of acylmethanes (methyl ketones), RCOCH3 (R = i-Pr, 1; Et, 2; Me, 3) with aryltellurium trichlorides, ArTeCl3 (Ar = 1-C10H7, Np, A; 2,4,6-Me3C6H2, Mes, B; 4-MeOC6H4, Anisyl, C) under mild conditions affords the corresponding acylmethyl(aryl)tellurium dichlorides (RCOCH2)ArTeCl2. Reduction of the dichlorides, gives tellurides, (i-PrCOCH2)ArTe, 1A-1C, which give the corresponding dihalides, (i-PrCOCH2)ArTeX2 (X = Cl, 1Aa-1Ca; Br, 1Ab-1Cb; I, 1Ac-1Cc) when reacted in situ with SO2Cl2, Br2 or I2. The unsymmetric tellurides are labile towards disproportionation and attempts to obtain them lead to the isolation of Ar2Te2 except in the case of (i-PrCOCH2)MesTe (1B), which represents an interesting example of a kinetically stable aryl(alkyl)telluride. All the dihalomesityltellurium(IV) derivatives show separate 1H and 13C NMR signals for the ortho methyls irrespective of the sizes of R and X ligands. The telluride, 1B with free rotation about Te-C(mesityl) bond shows, like the unsymmetric diorganotellurium(IV) dihalides, only one 125Te NMR signal. The 1,4-chelating behavior of the acyl ligand among diorganotellurium(IV) compounds is inferred from the X-ray diffraction data for 1Aa, 1Ac, 1Ba, 1Bb, 1cA and 1Cc which are indicative of the presence of intramolecular Te...O secondary bonding interactions (SBIs) at least in the solid state. As a consequence, steric repulsion in case of the mesityltellurium(IV) derivatives, 1Ba and 1Bb, reaches the threshold so as to cause loss of two-fold rotational symmetry of the mesityl group about the Te-C(mesityl) bond axis. Intermolecular C-HO...O H-bonding interactions appears to stabilize such an orientation of the aryl ligand at least in the solid state. PMID:18648706

  17. Acylmethyl(aryl)tellurium(IV,II) derivatives: intramolecular secondary bonding and steric rigidity.

    PubMed

    Chauhan, Ashok K S; Singh, Puspendra; Srivastava, Ramesh C; Duthie, Andrew; Voda, Andreea

    2008-08-14

    Electrophilic substitution of acylmethanes (methyl ketones), RCOCH3 (R = i-Pr, 1; Et, 2; Me, 3) with aryltellurium trichlorides, ArTeCl3 (Ar = 1-C10H7, Np, A; 2,4,6-Me3C6H2, Mes, B; 4-MeOC6H4, Anisyl, C) under mild conditions affords the corresponding acylmethyl(aryl)tellurium dichlorides (RCOCH2)ArTeCl2. Reduction of the dichlorides, gives tellurides, (i-PrCOCH2)ArTe, 1A-1C, which give the corresponding dihalides, (i-PrCOCH2)ArTeX2 (X = Cl, 1Aa-1Ca; Br, 1Ab-1Cb; I, 1Ac-1Cc) when reacted in situ with SO2Cl2, Br2 or I2. The unsymmetric tellurides are labile towards disproportionation and attempts to obtain them lead to the isolation of Ar2Te2 except in the case of (i-PrCOCH2)MesTe (1B), which represents an interesting example of a kinetically stable aryl(alkyl)telluride. All the dihalomesityltellurium(IV) derivatives show separate 1H and 13C NMR signals for the ortho methyls irrespective of the sizes of R and X ligands. The telluride, 1B with free rotation about Te-C(mesityl) bond shows, like the unsymmetric diorganotellurium(IV) dihalides, only one 125Te NMR signal. The 1,4-chelating behavior of the acyl ligand among diorganotellurium(IV) compounds is inferred from the X-ray diffraction data for 1Aa, 1Ac, 1Ba, 1Bb, 1cA and 1Cc which are indicative of the presence of intramolecular Te...O secondary bonding interactions (SBIs) at least in the solid state. As a consequence, steric repulsion in case of the mesityltellurium(IV) derivatives, 1Ba and 1Bb, reaches the threshold so as to cause loss of two-fold rotational symmetry of the mesityl group about the Te-C(mesityl) bond axis. Intermolecular C-HO...O H-bonding interactions appears to stabilize such an orientation of the aryl ligand at least in the solid state.

  18. Electronic and steric influences of pendant amine groups on the protonation of molybdenum bis (dinitrogen) complexes

    SciTech Connect

    Labios, Liezel A.; Heiden, Zachariah M.; Mock, Michael T.

    2015-05-04

    The synthesis of a series of PEtPNRR' (PEtPNRR' = Et₂PCH₂CH₂P(CH₂NRR')₂, R = H, R' = Ph or 2,4-difluorophenyl; R = R' = Ph or iPr) diphosphine ligands containing mono- and disubstituted pendant amine groups, and the preparation of their corresponding molybdenum bis(dinitrogen) complexes trans-Mo(N₂)₂(PMePh₂)₂(PEtPNRR') is described. In situ IR and multinuclear NMR spectroscopic studies monitoring the stepwise addition of (HOTf) to trans-Mo(N₂)₂(PMePh₂)₂(PEtPNRR') complexes in THF at -40 °C show that the electronic and steric properties of the R and R' groups of the pendant amines influence whether the complexes are protonated at Mo, a pendant amine, a coordinated N2 ligand, or a combination of these sites. For example, complexes containing mono-aryl substituted pendant amines are protonated at Mo and pendant amine to generate mono- and dicationic Mo–H species. Protonation of the complex containing less basic diphenyl-substituted pendant amines exclusively generates a monocationic hydrazido (Mo(NNH₂)) product, indicating preferential protonation of an N₂ ligand. Addition of HOTf to the complex featuring more basic diisopropyl amines primarily produces a monocationic product protonated at a pendant amine site, as well as a trace amount of dicationic Mo(NNH₂) product that contain protonated pendant amines. In addition, trans-Mo(N₂)₂(PMePh₂)₂(depe) (depe = Et₂PCH₂CH₂PEt₂) without a pendant amine was synthesized and treated with HOTf, generating a monocationic Mo(NNH₂) product. Protonolysis experiments conducted on select complexes in the series afforded trace amounts of NH₄⁺. Computational analysis of the series of trans-Mo(N₂)₂(PMePh₂)₂(PEtPNRR') complexes provides further insight into the proton affinity values of the metal center, N₂ ligand, and pendant amine sites to rationalize

  19. Overcoming the obstacles: Life stories of scientists with learning disabilities

    NASA Astrophysics Data System (ADS)

    Force, Crista Marie

    Scientific discovery is at the heart of solving many of the problems facing contemporary society. Scientists are retiring at rates that exceed the numbers of new scientists. Unfortunately, scientific careers still appear to be outside the reach of most individuals with learning disabilities. The purpose of this research was to better understand the methods by which successful learning disabled scientists have overcome the barriers and challenges associated with their learning disabilities in their preparation and performance as scientists. This narrative inquiry involved the researcher writing the life stories of four scientists. These life stories were generated from extensive interviews in which each of the scientists recounted their life histories. The researcher used narrative analysis to "make sense" of these learning disabled scientists' life stories. The narrative analysis required the researcher to identify and describe emergent themes characterizing each scientist's life. A cross-case analysis was then performed to uncover commonalities and differences in the lives of these four individuals. Results of the cross-case analysis revealed that all four scientists had a passion for science that emerged at an early age, which, with strong drive and determination, drove these individuals to succeed in spite of the many obstacles arising from their learning disabilities. The analysis also revealed that these scientists chose careers based on their strengths; they actively sought mentors to guide them in their preparation as scientists; and they developed coping techniques to overcome difficulties and succeed. The cross-case analysis also revealed differences in the degree to which each scientist accepted his or her learning disability. While some demonstrated inferior feelings about their successes as scientists, still other individuals revealed feelings of having superior abilities in areas such as visualization and working with people. These individuals revealed

  20. The immunological barriers to xenotransplantation.

    PubMed

    Vadori, M; Cozzi, E

    2015-10-01

    The availability of cells, tissues and organs from a non-human species such as the pig could, at least in theory, meet the demand of organs necessary for clinical transplantation. At this stage, the important goal of getting over the first year of survival has been reported for both cellular and solid organ xenotransplantation in relevant preclinical primate models. In addition, xenotransplantation is already in the clinic as shown by the broad use of animal-derived medical devices, such as bioprosthetic heart valves and biological materials used for surgical tissue repair. At this stage, however, prior to starting a wide-scale clinical application of xenotransplantation of viable cells and organs, the important obstacle represented by the humoral immune response will need to be overcome. Likewise, the barriers posed by the activation of the innate immune system and coagulative pathway will have to be controlled. As far as xenogeneic nonviable xenografts, increasing evidence suggests that considerable immune reactions, mediated by both innate and adaptive immunity, take place and influence the long-term outcome of xenogeneic materials in patients, possibly precluding the use of bioprosthetic heart valves in young individuals. In this context, the present article provides an overview of current knowledge on the immune processes following xenotransplantation and on the possible therapeutic interventions to overcome the immunological drawbacks involved in xenotransplantation.

  1. Puncture detecting barrier materials

    DOEpatents

    Hermes, Robert E.; Ramsey, David R.; Stampfer, Joseph F.; Macdonald, John M.

    1998-01-01

    A method and apparatus for continuous real-time monitoring of the integrity of protective barrier materials, particularly protective barriers against toxic, radioactive and biologically hazardous materials has been developed. Conductivity, resistivity or capacitance between conductive layers in the multilayer protective materials is measured by using leads connected to electrically conductive layers in the protective barrier material. The measured conductivity, resistivity or capacitance significantly changes upon a physical breach of the protective barrier material.

  2. Puncture detecting barrier materials

    DOEpatents

    Hermes, R.E.; Ramsey, D.R.; Stampfer, J.F.; Macdonald, J.M.

    1998-03-31

    A method and apparatus for continuous real-time monitoring of the integrity of protective barrier materials, particularly protective barriers against toxic, radioactive and biologically hazardous materials has been developed. Conductivity, resistivity or capacitance between conductive layers in the multilayer protective materials is measured by using leads connected to electrically conductive layers in the protective barrier material. The measured conductivity, resistivity or capacitance significantly changes upon a physical breach of the protective barrier material. 4 figs.

  3. Industry-College Cooperation: New Components, Barriers and Strategies.

    ERIC Educational Resources Information Center

    Rinehart, Richard L.

    A variety of linkage components that can help build and maintain effective relationships between the worlds of work and education are identified, and barriers to the development of such relationships and techniques for overcoming them are described in this report. The first section lists different forms of industry/education cooperation and their…

  4. Barriers to Healthier Eating in a Disadvantaged Community

    ERIC Educational Resources Information Center

    O'Neill, Martin; Rebane, Deanne; Lester, Carolyn

    2004-01-01

    Objective: The research objective was to identify how healthy eating was understood in a disadvantaged community and how barriers to healthy eating might be overcome. Design: Participatory action research. Setting: Communities in Gurnos, Merthyr Tydfil, one of the most deprived areas in the UK. Method: Trainees on a participative methods course…

  5. The Barriers Project.

    ERIC Educational Resources Information Center

    Confederation Coll. of Applied Arts and Technology, Thunder Bay (Ontario).

    In 1987, the Barriers Project was initiated by Confederation College of Applied Arts and Technology to engage 31 selected community colleges in Canada in an organized self-appraisal of institutional barriers to the enrollment of part-time credit students. From the outset, colleges were encouraged to limit their investigation to barriers over which…

  6. Steric and electronic effects of 1,3-disubstituted cyclopentadienyl ligands on metallocene derivatives of Cerium, Titanium, Manganese, and Iron

    SciTech Connect

    Sofield, C.D.

    2000-05-19

    Sterically demanding 1,3-disubstituted cyclopentadienyl ligands were used to modify the physical properties of the corresponding metallocenes. Sterically demanding ligands provided kinetic stabilization for trivalent cerium compounds. Tris(di-t-butylcyclopentadienyl)cerium was prepared and anion competition between halides and cyclopentadienyl groups which had complicated synthesis of the tris(cyclopentadienyl)compound was qualitatively examined. Bis(di-t-butylcyclopentadienyl)cerium methyl was prepared and its rate of decomposition, by ligand redistribution, to tris(di-t-butylcyclopentadienyl)cerium was shown to be slower than the corresponding rate for less sterically demanding ligands. Asymmetrically substituted ligands provided a symmetry label for examination of chemical exchange processes. Tris[trimethylsilyl(t-butyl)cyclopentadienyl]cerium was prepared and the rate of interconversion between the C1 and C3 isomers was examined. The enthalpy difference between the two distereomers is 7.0 kJ/mol. The sterically demanding cyclopentadienyl ligands ansa-di-t-butylcyclopentadiene (Me2Si[(Me3C)2C5H3]2), ansa-bis(trimethylsilyl)cyclopentadiene (Me2Si[(Me3Si)2C5H3]2) and tetra-t-butylfulvalene and metallocene derivatives of the ligands were prepared and their structures were examined by single crystal X-ray crystallography. The effect that substituents on the cyclopentadienyl ring have on the pi-electron system of the ligand was examined through interaction between ligand and metal orbitals. A series of 1,3-disubstituted manganocenes was prepared and their electronic states were determined by solid-state magnetic susceptibility, electron paramagnetic resonance, X-ray crystallography, and variable temperature UV-vis spectroscopy. Spin-equilibria in [(Me3C)2C5H3]2Mn and [(Me3C)(Me3Si)C5H3]2Mn were examined and indicate an enthalpy difference of 15 kJ/mol between the high-spin and low-spin forms. Cyclopentadienyl groups resistant to intramolecular oxidative addition

  7. Sterically-controlled intermolecular Friedel-Crafts acylation with twisted amides via selective N-C cleavage under mild conditions.

    PubMed

    Liu, Yongmei; Meng, Guangrong; Liu, Ruzhang; Szostak, Michal

    2016-05-21

    Highly chemoselective Friedel-Crafts acylation with twisted amides under mild conditions is reported for the first time. The reaction shows high functional group tolerance, obviating the need for preformed sensitive organometallic reagents and expensive transition metal catalysts. The high reactivity of amides is switched on by ground-state steric distortion to disrupt the amide bond nN→πCO* resonance as a critical design feature. Conceptually, this new acid-promoted mechanism of twisted amides provides direct access to bench-stable acylating reagents under mild, metal-free conditions. PMID:27139813

  8. An S(N)Ar approach to sterically hindered ortho-alkoxybenzaldehydes for the synthesis of olefin metathesis catalysts.

    PubMed

    Engle, Keary M; Luo, Shao-Xiong; Grubbs, Robert H

    2015-04-17

    A three-step procedure has been developed for preparing ortho-alkoxybenzaldehydes from ortho-fluorobenzaldehydes that tolerates the use of sterically hindered sodium alkoxide nucleophiles. The protocol is modular and operationally convenient. The ortho-alkoxybenzaldehyde products can be converted in one additional step to ortho-alkoxystyrenes by a Wittig reaction. These styrenes are precursors to the chelating benzylidene moiety in a proposed series of novel ruthenium complexes for use in olefin metathesis. Chelation with three representative styrenes has been demonstrated. PMID:25826714

  9. Total synthesis of hibispeptin A via Pd-catalyzed C(sp3)-H arylation with sterically hindered aryl iodides.

    PubMed

    He, Gang; Zhang, Shu-Yu; Nack, William A; Pearson, Ryan; Rabb-Lynch, Javon; Chen, Gong

    2014-12-19

    To access the key Ile-Hpa pseudodipeptide motif in hibispeptins, a series of bidentate carboxamide-based auxiliary groups have been explored to facilitate the palladium-catalyzed arylation of unactivated γ-C(sp(3))-H bonds of Ile precursor with aryl iodides. A new pyridylmethylamine-based auxiliary group PR is introduced, which permits the use of more sterically hindered ortho-substituted aryl iodide substrates and can be removed under mild conditions. Pd-catalyzed PR-directed γ-C(sp(3))-H arylation enabled the first total synthesis of hibispeptin A.

  10. An S(N)Ar approach to sterically hindered ortho-alkoxybenzaldehydes for the synthesis of olefin metathesis catalysts.

    PubMed

    Engle, Keary M; Luo, Shao-Xiong; Grubbs, Robert H

    2015-04-17

    A three-step procedure has been developed for preparing ortho-alkoxybenzaldehydes from ortho-fluorobenzaldehydes that tolerates the use of sterically hindered sodium alkoxide nucleophiles. The protocol is modular and operationally convenient. The ortho-alkoxybenzaldehyde products can be converted in one additional step to ortho-alkoxystyrenes by a Wittig reaction. These styrenes are precursors to the chelating benzylidene moiety in a proposed series of novel ruthenium complexes for use in olefin metathesis. Chelation with three representative styrenes has been demonstrated.

  11. On the impact of steric and electronic properties of ligands on gold(I)-catalyzed cycloaddition reactions.

    PubMed

    Benitez, Diego; Tkatchouk, Ekaterina; Gonzalez, Ana Z; Goddard, William A; Toste, F Dean

    2009-11-01

    It is shown that [4 + 3] and [4 + 2] cycloaddition pathways are accessible in the Au(I) catalysis of allene-dienes. Seven-membered ring gold-stabilized carbenes, originating from the [4 + 3] cycloaddition process, are unstable and can rearrange via a 1,2-H or a 1,2-alkyl shift to yield six- and seven-membered products. Both steric and electronic properties of the AuL(+) catalyst affect the electronic structure of the intermediate gold-stabilized carbene and its subsequent reactivity.

  12. Barriers to Successful Implementation of Technology Integration in Educational Settings: A Case Study

    ERIC Educational Resources Information Center

    Laferrière, T.; Hamel, C.; Searson, M.

    2013-01-01

    Representing issues discussed at the EduSummIT 2011 relative to essential conditions and barriers to successful technology integration, this article presents a systemic analysis of barriers that needed to be overcome for an information technology initiative (Remote Networked School project) to be successfully implemented. The analysis was…

  13. Development of the Motivators of and Barriers to Health-Smart Behaviors Inventory

    ERIC Educational Resources Information Center

    Tucker, Carolyn M.; Rice, Kenneth G.; Hou, Wei; Kaye, Lillian B.; Nolan, Sarah E. M.; Grandoit, Delphia J.; Gonzales, Lucia; Smith, Mary B.; Desmond, Frederic F.

    2011-01-01

    The Motivators of and Barriers to Health-Smart Behaviors Inventory (MB-HSBI) was developed for use in identifying self-reported motivators of and barriers to the following health-promoting behaviors (called "health-smart behaviors") that should occur daily to help promote health and overcome illnesses/diseases: eating a healthy breakfast, eating…

  14. Barriers and Strategies for Success for American Indian College Students: A Review

    ERIC Educational Resources Information Center

    Keith, Jill F.; Stastny, Sherri N.; Brunt, Ardith

    2016-01-01

    American Indian and Alaska Native students have a significantly lower college graduation rate than that of other ethnic groups in the United States. These students often face a variety of barriers to the completion of their education. Overcoming barriers for the achievement of an advanced education takes commitment, hard work, and dedication on…

  15. Traditional Barriers to Educational Opportunity: Unserved/Underserved Children and Young People in Special Education.

    ERIC Educational Resources Information Center

    Taylor, Steven J.; And Others

    Barriers to providing an appropriate public education to all children with handicaps are analyzed, and promising practices are identified to counter the effect of each. Nonbiased assessment procedures, vocational or educational curricula, and related services are seen as critical aspects in overcoming technological barriers, while attitude…

  16. Overcoming Old in Age-Friendliness

    PubMed Central

    Lindenberg, J.; Westendorp, R.G.J.

    2015-01-01

    In this article, we explore views on an age-friendly space in the Netherlands by analysing the responses of older individuals (N = 54) in focus groups and by examining the perspectives around an age-friendly zone in the Netherlands, Parkstad Limburg. We found that a central issue in the wishes for living at a later age are adjustments to envisioned physical limitations that come with the ageing process; this includes adjustments to ensure safety, accessibility and mobility, in order to facilitate older individuals' efforts to stay engaged with the world around them. In their wishes, the older participants constructed ideal dwelling places that closely resembled a senior home, but at the same time they rejected wishing to live in a place that was identified as a senior home. We explain this paradox by the representation of such a space as being for old people, i.e. needy older individuals, which was not how the older participants wished to be identified. We conclude that the conception of age-friendly environments will have to face the difficult challenge of overcoming the association with old age, while simultaneously taking into account adjustments that signify and relate to the ageing process and that seem inescapably tied to oldness. PMID:26028795

  17. Nanopreparations to overcome multidrug resistance in cancer.

    PubMed

    Patel, Niravkumar R; Pattni, Bhushan S; Abouzeid, Abraham H; Torchilin, Vladimir P

    2013-11-01

    Multidrug resistance is the most widely exploited phenomenon by which cancer eludes chemotherapy. Broad variety of factors, ranging from the cellular ones, such as over-expression of efflux transporters, defective apoptotic machineries, and altered molecular targets, to the physiological factors such as higher interstitial fluid pressure, low extracellular pH, and formation of irregular tumor vasculature are responsible for multidrug resistance. A combination of various undesirable factors associated with biological surroundings together with poor solubility and instability of many potential therapeutic small & large molecules within the biological systems and systemic toxicity of chemotherapeutic agents has necessitated the need for nano-preparations to optimize drug delivery. The physiology of solid tumors presents numerous challenges for successful therapy. However, it also offers unique opportunities for the use of nanotechnology. Nanoparticles, up to 400 nm in size, have shown great promise for carrying, protecting and delivering potential therapeutic molecules with diverse physiological properties. In this review, various factors responsible for the MDR and the use of nanotechnology to overcome the MDR, the use of spheroid culture as well as the current technique of producing microtumor tissues in vitro are discussed in detail. PMID:23973912

  18. NANOPREPARATIONS TO OVERCOME MULTIDRUG RESISTANCE IN CANCER

    PubMed Central

    Patel, Niravkumar R.; Pattni, Bhushan S.; Abouzeid, Abraham H.; Torchilin, Vladimir P.

    2013-01-01

    Multidrug resistance is the most widely exploited phenomenon by which cancer eludes chemotherapy. Broad variety of factors, ranging from the cellular ones, such as over-expression of efflux transporters, defective apoptotic machineries, and altered molecular targets, to the physiological factors such as higher interstitial fluid pressure, low extracellular pH, and formation of irregular tumor vasculature are responsible for multidrug resistance. A combination of various undesirable factors associated with biological surroundings together with poor solubility and instability of many potential therapeutic small & large molecules within the biological systems and systemic toxicity of chemotherapeutic agents has necessitated the need for nano-preparations to optimize drug delivery. The physiology of solid tumors presents numerous challenges for successful therapy. However, it also offers unique opportunities for the use of nanotechnology. Nanoparticles, up to 400 nm in size, have shown great promise for carrying, protecting and delivering potential therapeutic molecules with diverse physiological properties. In this review, various factors responsible for the MDR and the use of nanotechnology to overcome the MDR, the use of spheroid culture as well as the current technique of producing micro tumor tissues in vitro are discussed in detail. PMID:23973912

  19. Cooperative networks overcoming defectors by social influence

    NASA Astrophysics Data System (ADS)

    Gomez Portillo, Ignacio

    2014-01-01

    We address the cooperation problem in structured populations by considering the prisoner’s dilemma game as a metaphor of the social interactions between individuals with imitation capacity. We present a new strategy update rule called democratic weighted update where the individual’s behavior is socially influenced by each one of their neighbors. In particular, the capacity of an individual to socially influence other ones is proportional to its accumulated payoff. When in a neighborhood there are cooperators and defectors, the focal player is contradictorily influenced by them and, therefore, the effective social influence is given by the difference of the accumulated payoff of each strategy in its neighborhood. First, by considering the growing process of the network and neglecting mutations, we show the evolution of highly cooperative systems. Then, we broadly show that the social influence allows to overcome the emergence of defectors into highly cooperative systems. In this way, we conclude that in a structured system formed by a growing process, the cooperation evolves if the individuals have an imitation capacity socially influenced by each one of their neighbors. Therefore, here we present a theoretical solution of the cooperation problem among genetically unrelated individuals.

  20. Extremal surface barriers

    NASA Astrophysics Data System (ADS)

    Engelhardt, Netta; Wall, Aron C.

    2014-03-01

    We present a generic condition for Lorentzian manifolds to have a barrier that limits the reach of boundary-anchored extremal surfaces of arbitrary dimension. We show that any surface with nonpositive extrinsic curvature is a barrier, in the sense that extremal surfaces cannot be continuously deformed past it. Furthermore, the outermost barrier surface has nonnegative extrinsic curvature. Under certain conditions, we show that the existence of trapped surfaces implies a barrier, and conversely. In the context of AdS/CFT, these barriers imply that it is impossible to reconstruct the entire bulk using extremal surfaces. We comment on the implications for the firewall controversy.